亚抑菌浓度抗生素对细菌耐药性和毒力影响的研究进展
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摘要
细菌的耐药性和毒力是决定抗生素治疗成败的关键。近年来研究表明亚抑菌浓度抗生素可以诱导细菌耐药并影响细菌的毒力。本文介绍了亚抑菌浓度抗生素产生的来源;阐述了亚抑菌浓度抗生素对细菌耐药性和毒力的影响。亚抑菌浓度抗生素对细菌耐药性的影响涉及了细菌的耐药选择性、生物被膜和持留菌的形成、基因突变、水平基因转移和基因表达;对细菌毒力的影响主要包括细菌的黏附性、运动性和其它毒力因子。以期为畜牧生产中减少和避免亚抑菌浓度抗菌药的产生,减缓和克服细菌耐药性,降低致病菌的毒力提供参考。
Antibacterial resistance and bacterial virulence is the key factor to determine the treatment effect of antibioticsis the determinant of whether the bacteria can infect the host. In recent years, the problem of antibacterial resistance has been paid attention, and the virulence of bacteria also causes widespread concern. The origins of subinhibitory concentration of antibiotics were introduced in this paper. Influences of sub-inhibitory concentration of antibiotics on the bacterial resistance and virulence were summarized. The effects of the sub-inhibitory concentration of antibiotics on bacterial resistance is related to the selective resistance, bio-film formation, persisters, gene mutation, horizontal gene transfer and gene expression. The effects of the sub-inhibitory concentration of antibiotics on bacterial virulence were also described, such as bacterial adhesion, motility and other virulence factors. This review aims to deliver the knowledge on the theoretical basis for reducing and avoiding the emergence of drug resistance regarding the sub-inhibitory concentration in livestock production, to slow down and overcome drug resistance and to reduce the virulence of pathogenic bacteria.
Antibacterial resistance and bacterial virulence is the key factor to determine the treatment effect of antibioticsis the determinant of whether the bacteria can infect the host. In recent years, the problem of antibacterial resistance has been paid attention, and the virulence of bacteria also causes widespread concern. The origins of subinhibitory concentration of antibiotics were introduced in this paper. Influences of sub-inhibitory concentration of antibiotics on the bacterial resistance and virulence were summarized. The effects of the sub-inhibitory concentration of antibiotics on bacterial resistance is related to the selective resistance, bio-film formation, persisters, gene mutation, horizontal gene transfer and gene expression. The effects of the sub-inhibitory concentration of antibiotics on bacterial virulence were also described, such as bacterial adhesion, motility and other virulence factors. This review aims to deliver the knowledge on the theoretical basis for reducing and avoiding the emergence of drug resistance regarding the sub-inhibitory concentration in livestock production, to slow down and overcome drug resistance and to reduce the virulence of pathogenic bacteria.
引文
[1]Stolker A A,Manti V,Zuidema T,et al.Carry-over of veterinary drugs from medicated to non-medicated feeds in commercial feed manufacturing plants[J].Food Additi Contam,2013,30(6):1100-1107.
[2]Atkinson B A,Amaral L,Washington J A.Sublethal concentrations of antibiotics,effects on bacteria and the immune system[J].Crc Crit Rev Microbiol,1982,9(2):101-138.
[3]Lillicrap A,Macken A,Wennberg A C,et al.Environmental fate and effects of novel quorum sensing inhibitors that can control biofilm formation[J].Chemosph,2016,164:52-58.
[4]He S,Gallert C.Growth Behavior of E.coli,Enterococcus and Staphylococcus species in the presence and absence of sub-inhibitory antibiotic concentrations:Consequences for interpretation of culture-based data[J].Microbial Ecol,2016,72(4):1-11.
[5]Roch M,Clair P,Rtaphylococcus aureus to subinhibitory concentrations of beta-lactam antibiotics induces heterogeneous vancomycinintermediate Staphylococcus aureus[J].Antimicrob Agents Chemother,2014,58(9):5306-5314.
[6]J?rgensen K M,Wassermann T,Jensen P?,et al.Sublethal ciprofloxacin treatment leads to rapid development of highlevel ciprofloxacin resistance during long-term experimental evolution of Pseudomonas aeruginosa[J].Antimicrob Agents Chemother,2013,57(9):4215-4221.
[7]Dal Sasso M,Culici M,Bovio C,et al.Gemifloxacin:Effects of sub-inhibitory concentrations on various factors affecting bacterial virulence[J].Int J Antimicrob Agents,2003,21(4):325-333.
[8]Dal Sasso M,Bovio C,Culici M,et al.Interference of sub-inhibitory concentrations of gatifloxacin on various determinants of bacterial virulence[J].J Chemother,2002,14(5):473-482.
[9]Friman V P,Guzman L M,Reuman D C,et al.Bacterial adaptation to sublethal antibiotic gradients can change the ecological properties of multitrophic microbial communities[J].Proc Biolog Sci,2015,282(1806):20142920.
[10]Westhoff S,Leeuwe T M V,Qachach O,et al.The evolution of no-cost resistance at sub-MIC concentrations of streptomycin in Streptomyces coelicolor[J].Isme J,2016,11(5):1168-1178.
[11]Cheng G Y,Hao H H,Xie S Y,et al.Antibiotic alternatives:The substitution of antibiotics in animal husbandry[J].Front Microbiol,2014,5(2):217-231.
[12]Hao H H,Cheng G Y,Iqbal Z,et al.Benefits and risks of antimicrobial use in food-producing animals[J].Front Microbiol,2014,5(7):288-298.
[13]Cheng G,Dai M,Ahmed S,et al.Antimicrobial drugs in fighting against antimicrobial resistance[J].Front Microbiol,2016,7:832-842.
[14]Cairns J,Becks L,Jalasvuori M,et al.Sublethal streptomycin concentrations and lytic bacteriophage together promote resistance evolution[J].Philos Trans R Soc Lond BBiol Sci,2017,372(1712):20160040.
[15]Erik G,Sha C,Otto G B,et al.Selection of resistant bacteria at very low antibiotic concentrations[J].PLoS Pathogens,2011,7(7):e1002158.
[16]Andersson D I,Hughes D.Evolution of antibiotic resistance at non-lethal drug concentrations[J].Drug Resist Updates,2012,15(3):162-172.
[17]程古月,郝海红,戴梦红,等.病原菌的群体感应及其抑制剂的研究进展[J].科学通报,2012,57(21):1964-1977.
[18]Hoffman L R,D'argenio D A,Maccoss M J,et al.Aminoglycoside antibiotics induce bacterial biofilm formation[J].Nature,2005,436(7054):1171-1175.
[19]Weiser J,Henke H A,Hector N,et al.Sub-inhibitory tigecycline concentrations induce extracellular matrix epidermidis biofilm formation and immune evasion[J].Int JMed Microbiol,2016,306(6):471-478.
[20]Sudarat B,Sutthirat S,Duangkamol K.In vitro interference of cefotaxime at subinhibitory concentrations on biofilm formation by nontypeable Haemophilus influenzae[J].Asian Pacific J Trop Biomed,2016,6(9):745-750.
[21]Van Laar T A,Chen T,You T,et al.Sublethal concentrations of carbapenems alter cell morphology and genomic expression of Klebsiella pneumoniae biofilms[J].Antimicrob Agents Chemother,2015,59(3):1707-1717.
[22]Silva J O,Martins Reis A C,Quesada-Gómez C,et al.In vitro effect of antibiotics on biofilm formation by Bacteroides fragilis group strains isolated from intestinal microbiota of dogs and their antimicrobial susceptibility[J].Anaerobe,2014,28C:24-28.
[23]Hathroubi S,Fontaine-Gosselin Sè,Tremblay Y D N,et al.Subinhibitory concentrations of penicillin G induce biofilm formation by field isolates of Actinobacillus pleuropneumoniae[J].Veterin microbiol,2015,179(3-4):277-286.
[24]Molina-Quiroz R C,Silva C A,Molina C F,et al.Exposure to sub-inhibitory concentrations of cefotaxime enhances the systemic colonization of Salmonella Typhimurium in BALB/c mice[J].Open Biol,2015,5(10):pii:150070.
[25]He H J,Sun F J,Wang Q,et al.Original article:Erythromycin resistance features and biofilm formation affected by subinhibitory erythromycin in clinical isolates of Staphylococcus epidermidis[J].J Microbiol Immunol Infect,2014,49(1):33-40.
[26]Kumar A,Ting Y P.Effect of sub-inhibitory antibacterial stress on bacterial surface properties and biofilm formation[J].Coll Surf B Bioint,2013,111(6):747-754.
[27]BalaguéC,Pérez J,Rinaudo M,et al.Inhibition of the adhesion to catheters of uropathogenic Escherichia coli by sub-inhibitory concentrations of cefotaxime[J].Eur J Obstet Gynecol Reprod Biol,2011,155(2):150-156.
[28]Bruchmann J,Kirchen S,Schwartz T.Sub-inhibitory concentrations of antibiotics and wastewater influencing biofilm formation and gene expression of multi-resistant Pseudomonas aeruginosa wastewater isolates[J].Environ Sci Poll Res,2013,20(6):3539-3549.
[29]Jones C,Allsopp L,Horlick J,et al.Subinhibitory concentration of kanamycin induces the Pseudomonas aeruginosa type VI secretion system[J].PloS one,2013,8(11):e81132.
[30]Martinez J L.Drug resistance:General principles of antibiotic resistance in bacteria[J].Drug Discov Today:Technol,2014,11:33-39.
[31]Wang S,Yang Y,Zhao Y,et al.Sub-MIC Tylosin Inhibits Streptococcus suis biofilm formation and results in differential protein expression[J].Front Microbiol,2016,7:384-392.
[32]Kwiecńskapiróg J,Skowron K,Zniszczol K,et al.The assessment of Proteus mirabilis susceptibility to ceftazidime and ciprofloxacin and the impact of these antibiotics at subinhibitory concentrations on Proteus mirabilis biofilms[J].Bio Med Res Int,2013,2013(6):930876.
[33]Nguyen U T,Harvey H,Hogan A J,et al.Role of PBPD1in stimulation of listeria monocytogenes biofilm formation by subminimal inhibitoryβ-lactam concentrations[J].Antimicrob Agents Chemother,2014,58(11):6508-6517.
[34]Haddadin R N,Saleh S,Adham I S,et al.The effect of subminimal inhibitory concentrations of antibiotics on virulence factors expressed by Staphylococcus aureus biofilms[J].J Appl Microbiol,2010,108(4):1281-1291.
[35]Balaji K,Thenmozhi R,Pandian S K.Effect of subinhibitory concentrations of fluoroquinolones on biofilm production by clinical isolates of Streptococcus pyogenes[J].Ind J Med Res,2013,137(5):963-971.
[36]Aka S T,Haji S H.Sub-MIC of antibiotics induced biofilm formation of Pseudomonas aeruginosa in the presence of chlorhexidine[J].Brazil J Microbiol:Publ Brazil Soci Microbiol,2015,46(1):149-154.
[37]De Souza Filho J A,Diniz C G,Barbosa N B,et al.Clinical microbiology:Morphological,biochemical,physiological and molecular aspects of the response of Fusobacterium nucleatum exposed to subinhibitory concentrations of antimicrobials[J].Anaerobe,2012,18(6):566-575.
[38]Maioli E,Marchese A,Roveta S,et al.In vitro activity of ceftibuten at sub-inhibitory concentrations in comparison with other antibiotics against respiratory and urinary tract pathogens[J].J Chemother,2014,19(2):152-160.
[39]Liu Z,Wang W,Zhu Y,et al.Antibiotics at subinhibitory concentrations improve the quorum sensing behavior of Chromobacterium violaceum[J].Fems Microbiol Lett,2013,341(1):37-44.
[40]Dorota W,Dorota T.Effect of sub-minimum inhibitory concentrations of ciprofloxacin,amikacin and colistin on biofilm formation and virulence factors of Escherichia coli planktonic and biofilm forms isolated from human urine[J].Lasers Electro-optics,2013,23(6):7471-7480.
[41]Ara J,Juhee A.Phenotypic and genotypic characterisation of multiple antibiotic-resistant Staphylococcus aureus exposed to subinhibitory levels of oxacillin and levofloxacin[J].Bmc Microbiol,2016,16(1):170-179.
[42]Kaplan J B,Jabbouri S,Sadovskaya I.Extracellular DNA-dependent biofilm formation by Staphylococcus epidermidis RP62A in response to subminimal inhibitory concentrations of antibiotics[J].Res Microbiol,2011,162(5):535-541.
[43]Husain F M,Ahmad I,Baig M H,et al.Broad-spectrum inhibition of AHL-regulated virulence factors and biofilms by sub-inhibitory concentrations of ceftazidime[J].RSCAdvan,2016,6(33):27952-27962.
[44]Starner T D,Shrout J D,Parsek M R,et al.Subinhibitory concentrations of azithromycin decrease nontypeable Haemophilus influenzae biofilm formation and Diminish established biofilms[J].Antimicrob Agents Chemother,2008,52(1):137-145.
[45]Roudashti S,Zeighami H,Mirshahabi H,et al.Synergistic activity of sub-inhibitory concentrations of curcumin with ceftazidime and ciprofloxacin against Pseudomonas aeruginosa quorum sensing related genes and virulence traits[J].World Jo Microbiol Biotechnol,2017,33(3):50-57.
[46]Li X Y,Xue F,Yang W W,et al.Effects of the subinhibitory concentration of levofloxacin promote virulence factor production of Pseudomonas aeruginosa[J].Chin J Clin Pharmacol,2013,5(163):355-357.
[47]Sophie H,Elisabeth K.Bacterial persisters:Formation,eradication,and experimental systems[J].Trends Microbiol,2014,22(7):417-424.
[48]Johnson P J T,Levin B R.Pharmacodynamics,population dynamics,and the evolution of persistence in Staphylococcus aureus[J].Plos Genetics,2013,9(1):e1003123.
[49]Dorr T,Lewis K,Vulic M.SOS Response induces persistence to fluoroquinolones in Escherichia coli[J].Plos Genetics,2009,5(12):e1000760.
[50]Hnternalization of Salmonella by macrophages induces formation of nonreplicating persisters[J].Science,2014,343(6167):204-208.
[51]Baharoglu Z,Mazel D.Vibrio cholerae triggers SOS and mutagenesis in response to a wide range of antibiotics:A route towards multiresistance[J].Antimicrob Agents Chemother,2011,55(5):2438-2441.
[52]Beaber J W,Hochhut B,Waldor M K.SOS response promotes horizontal dissemination of antibiotic resistance genes[J].Nature,2004,427(6969):72-74.
[53]Lopez E,Elez M,Matic I,et al.Antibiotic-mediated recombination:Ciprofloxacin stimulates SOS-independent recombination of divergent sequences in Escherichia coli[J].Molecul Microbiol,2007,64(1):83-93.
[54]Sandegren L,Dan I A.Bacterial gene amplification:Implications for the evolution of antibiotic resistance[J].Nat Rev Microbiol,2009,7(8):578-588.
[55]Gutierrez A,Laureti L,Crussard S,et al.Beta-lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity[J].Nat Communicat,2013,4:1610-1618.
[56]Nair C G,Chao C,Ryall B,et al.Sub-lethal concentrations of antibiotics increase mutation frequency in the cystic fibrosis pathogen Pseudomonas aeruginosa[J].Lett In Appl Microbiol,2013,56(2):149-154.
[57]Louise E,Liette E,Michael E.Potential impacts of aquatic pollutants:Sub-clinical antibiotic concentrations induce genome changes and promote antibiotic resistance[J].Front Microbiol,2015,6(803):803-812.
[58]Henderson-Begg S K,Livermore D M,Hall L M.Effect of subinhibitory concentrations of antibiotics on mutation frequency in Streptococcus pneumoniae[J].J Antimicrob Chemother,2006,57(5):849-854.
[59]Wang P,Zhang X N,Wang L,et al.Subinhibitory concentrations of ciprofloxacin induce SOS response and mutations of antibiotic resistance in bacteria[J].Ann Microbiol,2010,60(3):511-517.
[60]Roch M,Clataphylococcus aureus to subinhibitory concentrations ofβ-lactam antibiotics induces heterogeneous vancomycinintermediate Staphylococcus aureus[J].Antimicrob Agents Chemother,2014,58(9):5306-5314.
[61]Balaji K,Thenmozhi R,Pandian S K.Effect of subinhibitory concentrations of fluoroquinolones on biofilm production by clinical isolates of Streptococcus pyogenes[J].Ind J Med Res,2013,137(5):963-971.
[62]Shen S,Zhang T,Yuan Y,et al.Effects of cinnamaldehyde on Escherichia coli and Staphylococcus aureus membrane[J].Food Control,2015,47(47):196-202.
[63]Cortes P,Pinas G O A,Echenique J,et al.Subinhibitory concentrations of penicillin increase the mutation rate to optochin resistance in Streptococcus pneumoniae[J].JAntimicrob Chemother,2008,62(5):973-977.
[64]Goh E B,Yim G,Tsui W,et al.Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics[J].Proceed Nat Acad Scie USA,2002,99(26):17025.
[65]Garima K,Pathak R,Tandon R,et al.Differential expression of efflux pump genes of Mycobacterium tuberculosis in response to varied subinhibitory concentrations of antituberculosis agents[J].Tubercul,2015,95(2):155-161.
[66]Marti E,Huerta B,Rodríguezmozaz S,et al.Effects of subinhibitory ciprofloxacin concentrations on the abundance of qnrS and composition of bacterial communities from water supply reservoirs[J].Chemosphere,2016,161:470-474.
[67]Tattevin P,Basuino L,Chambers H F.Subinhibitory fluoroquinolone exposure selects for reduced beta-lactam susceptibility in methicillin-resistant Staphylococcus aureus and alterations in the SOS-mediated response[J].Res Microbiol,2009,160(3):187-92.
[68]Hua X T,Chen Q,Li X,et al.Global transcriptional response of Acinetobacter baumannii to a subinhibitory concentration of tigecycline[J].Int J Antimicrob Agents,2014,44(4):337-344.
[69]Cheng G Y,Hao H H,Dai M H,et al.Antibacterial action of quinolones:From target to network[J].Europ J Med Chem,2013,44(42):555-562.
[70]López E,Elez M,Matic I,et al.Antibiotic-mediated recombination:ciprofloxacin stimulates SOS-independent recombination of divergent sequences in Escherichia coli[J].Molecul Microbiol,2007,64(1):83-93.
[71]Jutkina J,Rutgersson C,Flach C F,et al.An assay for determining minimal concentrations of antibiotics that drive horizontal transfer of resistance[J].Sci Total Environ,2016,548-549:131-138.
[72]Brown S P,Cornforth D M,Mideo N.Evolution of virulence in opportunistic pathogens:generalism,plasticity,and control[J].Trends Microbiol,2012,20(7):336-342.
[73]Andrade J P,Farias L,Ferreira J F,et al.Sub-inhibitory concentration of piperacillin-tazobactam may be related to virulence properties of filamentous Escherichia coli[J].Curr Microbiol,2016,72(1):19-28.
[74]Sachdeva M,Leeds J A.Subinhibitory concentrations of LFF571 reduce toxin production by Clostridium difficile[J].Antimicrob Agents Chemother,2015,59(2):1252-1257.
[75]Ismaeel A Y,Senok A C,Bindayna K M,et al.Effect of antibiotic sub inhibitory concentration on cytolethal distending toxin production by Campylobacter jejuni[J].JInfect,2005,51(2):144-149.
[76]Haddadin R N,Saleh S,Aladham I S,et al.The effect of subminimal inhibitory concentrations of antibiotics on virulence factors expressed by Staphylococcus aureus biofilms[J].J Appl Microbiol,2010,108(4):1281-1291.
[77]Li D M,Renzoni A,Estoppey T,et al.Induction of fibronectin adhesins in quinolone-resistant Staphylococcus aureus by subinhibitory levels of ciprofloxacin or by sigma B transcription factor activity is mediated by two separate pathways[J].Antimicrob Agents Chemother,2005,49(3):916-924.
[78]Furneri P M,Garozzo A,Musumarra M P,et al.Effects on adhesiveness and hydrophobicity of sub-inhibitory concentrations of netilmicin[J].Int J Antimicrob Agents,2003,22(2):164-167.
[79]Gallardo-Moreno A M,Van Der Mei H C,Busscher H J,et al.Adhesion of Enterococcus faecalis 1131 grown under subinhibitory concentrations of ampicillin and vancomycin to a hydrophilic and a hydrophobic substratum[J].Fems Microbiol Lett,2001,203(1):75-79.
[80]Sinel C,Cacaci M,Meignen P,et al.Subinhibitory concentrations of ciprofloxacin enhance antimicrobial resistance and pathogenicity of Enterococcus faecium[J].Antimicrobial Agents Chemother,2017,61(5):AAC.02763-16.
[81]Rasigade J P,Moulay A,Lhoste Y,et al.Impact of subinhibitory antibiotics on fibronectin-mediated host cell adhesion and invasion by Staphylococcus aureus[J].BMCMicrobiol,2011,11(1):263-271.
[82]Vidya K C,Mallya P S,Rao P S.Inhibition of bacterial adhesion by subinhibitory concentrations of antibiotics[J].Ind J Med Microbiol,2005,23(2):102-105.
[83]Ogaard A R,Bj?ro K,Bukholm G,et al.Pseudomonas aeruginosa virulence factors:modifications by subinhibitory concentrations of carbenicillin or gentamicin[J].1986,94(2):63-68.
[84]Dal S M,Bovio C,Culici M,et al.Interference of subinhibitory concentrations of gatifloxacin on various determinants of bacterial virulence[J].J Chemother,2002,14(5):473-482.
[85]Pompilio A,Catavitello C,Picciani C,et al.Subinhibitory concentrations of moxifloxacin decrease adhesion and biofilm formation of Stenotrophomonas maltophilia from cystic fibrosis[J].J Med Microbiol,2010,59(1):76-81.
[86]Wojnicz D,Klak M,Adamski R,et al.Influence of subinhibitory concentrations of amikacin and ciprofloxacin on morphology and adherence ability of uropathogenic strains[J].Folia Microbiol,2007,52(4):429-436.
[87]Shen L,ShI Y,Zhang D,et al.Modulation of secreted virulence factor genes by subinhibitory concentrations of antibiotics in Pseudomonas aeruginosa[J].J Microbiol,2008,46(4):441-447.
[88]B raga P,Subinhibitory concentrations of rufloxacin on bacterial virulence factors[J].Antimicrob Agents Chemother,1999,43(5):1013-1019.
[89]Miyamoto K N,Monteiro K M,Caumo K D S,et al.Supporting data for comparative proteomic analysis of Listeria monocytogenes ATCC 7644 exposed to a sublethal concentration of nisin[J].2015,119:230-237.
[90]Tsai S H,Lai H C,Hu S T.Subinhibitory doses of Aaminoglycoside antibiotics induce changes in the phenotype of Mycobacterium abscessus[J].Antimicrob Agents Chemother,2015,59(10):6161-6169.
[91]Parul G,Sanjay C,Kusum H.Subinhibitory concentration of ciprofloxacin targets quorum sensing system of Pseudomonas aeruginosa causing inhibition of biofilm formation&reduction of virulence[J].Ind J Med Res,2016,143(5):643-651.
[92]Zhuang Y,Chen W,Yao F,et al.Short-term pretreatment of sub-inhibitory concentrations of gentamycin inhibits the swarming motility of Escherichia coli by down-regulating the succinate dehydrogenase gene[J].Cellul Physiol Biochem,2016,39(4):1307-1316.
[93]Lagrou K,Peetermans W E,Jorissen M,et al.Subinhibitory concentrations of erythromycin reduce pneumococcal adherence to respiratory epithelial cells in vitro[J].JAntimicrob Chemother,2000,46(5):717-723.
[94]Molinari G,Guzmán C A,Pesce A,et al.Inhibition of Pseudomonas aeruginosa virulence factors by subinhibitory antibiotics[J].J Antimicrobial Chemother,1993,31(5):681-688.
[95]Joo H S,Chan J L,Cheung G Y C,et al.Subinhibitory concentrations of protein synthesis-inhibiting antibiotics promote increased expression of the agr virulence regulator and production of phenol-soluble modulin cytolysins in community-associated methicillin-resistant Staphylococcus aureus[J].Antimicrob Agents Chemother,2010,54(11):4942-4944.
[96]Ohlsen K,Ziebuhr W,Koller K P,et al.Effects of subinhibitory concentrations of antibiotics on alphatoxin(hla)gene expression of methicillin-sensitive and methicillin-resistant Staphylococcus aureus isolates[J].Antimicrob Agents Chemother,1998,42(11):2817-2823.
[97]Gottschalk S,Ingmer H,Thomsen L E.The lysine-peptoid hybrid LP5 maintain activity under physiological conditions and affects virulence gene expression in Staphylococcus aureus[J].Peptides,2016,78:24-29.
[98]Ara J,Juhee A.Phenotypic and genotypic characterisation of multiple antibiotic-resistant Staphylococcus aureus exposed to subinhibitory levels of oxacillin and levofloxacin[J].BMCMicrobiol,2016,16(1):170-179.
[99]Lazaro-Diez M,Remuzgo-Martinez S,RodriguezMirones C,et al.Effects of subinhibitory concentrations of ceftaroline on methicillin-resistant Staphylococcus aureus(MRSA)biofilms[J].PloS one,2016,11(1):e0147569.
[100]Lück P C,Schmitt J W,Hengerer A,et al.Subinhibitory concentrations of antimicrobial agents reduce the uptake of Legionella pneumophila into Acanthamoeba castellanii and U937 Cells by altering the expression of virulenceassociated antigens[J].Antimicrob Agents Chemother,1998,42(11):2870-2876.
[101]Debbia E A,Maioli E,Roveta S,et al.Effects of rifaximin on bacterial virulence mechanisms at supra-and sub-inhibitory concentrations[J].J Chemother,2008,20(2):186-194.
[102]De Moura T M,Campos F S,Caierao J,et al.Influence of a subinhibitory concentration of vancomycin on the in vitro expression of virulence-related genes in the vancomycinresistant Enterococcus faecalis[J].Revista Da Socied Brasileira De Med Trop,2015,48(5):617-621.
[103]Haas B,Grenier D.Impact of sub-inhibitory concentrations of amoxicillin on streptococcus suis capsule gene expression and inflammatory potential[J].Pathog,2016,5(2):37-49.
[104]Otto M P,Martin E,Badiou C,et al.Effects of subinhibitory concentrations of antibiotics on virulence factor expression by community-acquired methicillin-resistant Staphylococcus aureus[J].J Antimicrob Chemother,2013,68(7):1524-1532.
[105]Wassermann T,Jorgensen K M,Ivanyshyn K,et al.The phenotypic evolution of Pseudomonas aeruginosa populations changes in the presence of subinhibitory concentrations of ciprofloxacin[J].Microbiol,2016,162(5):865-875.
[106]Yim G,Wang H H,Davies J.Antibiotics as signaling molecules[J].Philosoph Transact Royal Soci London,2007,362(1483):1195-1200.
[107]Popat R,Crusz S A,Messina M,et al.Quorum-sensing and cheating in bacterial biofilms[J].Proceed Biolog Sci,2012,279(1748):4765-4771.
[108]Goo E,An J H,Kang Y,et al.Control of bacterial metabolism by quorum sensing[J].Trends Microbiol,2015,23(9):567-576.
[109]Rutherford S T,Bassler B L.Bacterial quorum sensing:Its role in virulence and possibilities for its control[J].Cold Spring Harbor Perspectives Med,2012,2(11):705-709.
[2]Atkinson B A,Amaral L,Washington J A.Sublethal concentrations of antibiotics,effects on bacteria and the immune system[J].Crc Crit Rev Microbiol,1982,9(2):101-138.
[3]Lillicrap A,Macken A,Wennberg A C,et al.Environmental fate and effects of novel quorum sensing inhibitors that can control biofilm formation[J].Chemosph,2016,164:52-58.
[4]He S,Gallert C.Growth Behavior of E.coli,Enterococcus and Staphylococcus species in the presence and absence of sub-inhibitory antibiotic concentrations:Consequences for interpretation of culture-based data[J].Microbial Ecol,2016,72(4):1-11.
[5]Roch M,Clair P,Rtaphylococcus aureus to subinhibitory concentrations of beta-lactam antibiotics induces heterogeneous vancomycinintermediate Staphylococcus aureus[J].Antimicrob Agents Chemother,2014,58(9):5306-5314.
[6]J?rgensen K M,Wassermann T,Jensen P?,et al.Sublethal ciprofloxacin treatment leads to rapid development of highlevel ciprofloxacin resistance during long-term experimental evolution of Pseudomonas aeruginosa[J].Antimicrob Agents Chemother,2013,57(9):4215-4221.
[7]Dal Sasso M,Culici M,Bovio C,et al.Gemifloxacin:Effects of sub-inhibitory concentrations on various factors affecting bacterial virulence[J].Int J Antimicrob Agents,2003,21(4):325-333.
[8]Dal Sasso M,Bovio C,Culici M,et al.Interference of sub-inhibitory concentrations of gatifloxacin on various determinants of bacterial virulence[J].J Chemother,2002,14(5):473-482.
[9]Friman V P,Guzman L M,Reuman D C,et al.Bacterial adaptation to sublethal antibiotic gradients can change the ecological properties of multitrophic microbial communities[J].Proc Biolog Sci,2015,282(1806):20142920.
[10]Westhoff S,Leeuwe T M V,Qachach O,et al.The evolution of no-cost resistance at sub-MIC concentrations of streptomycin in Streptomyces coelicolor[J].Isme J,2016,11(5):1168-1178.
[11]Cheng G Y,Hao H H,Xie S Y,et al.Antibiotic alternatives:The substitution of antibiotics in animal husbandry[J].Front Microbiol,2014,5(2):217-231.
[12]Hao H H,Cheng G Y,Iqbal Z,et al.Benefits and risks of antimicrobial use in food-producing animals[J].Front Microbiol,2014,5(7):288-298.
[13]Cheng G,Dai M,Ahmed S,et al.Antimicrobial drugs in fighting against antimicrobial resistance[J].Front Microbiol,2016,7:832-842.
[14]Cairns J,Becks L,Jalasvuori M,et al.Sublethal streptomycin concentrations and lytic bacteriophage together promote resistance evolution[J].Philos Trans R Soc Lond BBiol Sci,2017,372(1712):20160040.
[15]Erik G,Sha C,Otto G B,et al.Selection of resistant bacteria at very low antibiotic concentrations[J].PLoS Pathogens,2011,7(7):e1002158.
[16]Andersson D I,Hughes D.Evolution of antibiotic resistance at non-lethal drug concentrations[J].Drug Resist Updates,2012,15(3):162-172.
[17]程古月,郝海红,戴梦红,等.病原菌的群体感应及其抑制剂的研究进展[J].科学通报,2012,57(21):1964-1977.
[18]Hoffman L R,D'argenio D A,Maccoss M J,et al.Aminoglycoside antibiotics induce bacterial biofilm formation[J].Nature,2005,436(7054):1171-1175.
[19]Weiser J,Henke H A,Hector N,et al.Sub-inhibitory tigecycline concentrations induce extracellular matrix epidermidis biofilm formation and immune evasion[J].Int JMed Microbiol,2016,306(6):471-478.
[20]Sudarat B,Sutthirat S,Duangkamol K.In vitro interference of cefotaxime at subinhibitory concentrations on biofilm formation by nontypeable Haemophilus influenzae[J].Asian Pacific J Trop Biomed,2016,6(9):745-750.
[21]Van Laar T A,Chen T,You T,et al.Sublethal concentrations of carbapenems alter cell morphology and genomic expression of Klebsiella pneumoniae biofilms[J].Antimicrob Agents Chemother,2015,59(3):1707-1717.
[22]Silva J O,Martins Reis A C,Quesada-Gómez C,et al.In vitro effect of antibiotics on biofilm formation by Bacteroides fragilis group strains isolated from intestinal microbiota of dogs and their antimicrobial susceptibility[J].Anaerobe,2014,28C:24-28.
[23]Hathroubi S,Fontaine-Gosselin Sè,Tremblay Y D N,et al.Subinhibitory concentrations of penicillin G induce biofilm formation by field isolates of Actinobacillus pleuropneumoniae[J].Veterin microbiol,2015,179(3-4):277-286.
[24]Molina-Quiroz R C,Silva C A,Molina C F,et al.Exposure to sub-inhibitory concentrations of cefotaxime enhances the systemic colonization of Salmonella Typhimurium in BALB/c mice[J].Open Biol,2015,5(10):pii:150070.
[25]He H J,Sun F J,Wang Q,et al.Original article:Erythromycin resistance features and biofilm formation affected by subinhibitory erythromycin in clinical isolates of Staphylococcus epidermidis[J].J Microbiol Immunol Infect,2014,49(1):33-40.
[26]Kumar A,Ting Y P.Effect of sub-inhibitory antibacterial stress on bacterial surface properties and biofilm formation[J].Coll Surf B Bioint,2013,111(6):747-754.
[27]BalaguéC,Pérez J,Rinaudo M,et al.Inhibition of the adhesion to catheters of uropathogenic Escherichia coli by sub-inhibitory concentrations of cefotaxime[J].Eur J Obstet Gynecol Reprod Biol,2011,155(2):150-156.
[28]Bruchmann J,Kirchen S,Schwartz T.Sub-inhibitory concentrations of antibiotics and wastewater influencing biofilm formation and gene expression of multi-resistant Pseudomonas aeruginosa wastewater isolates[J].Environ Sci Poll Res,2013,20(6):3539-3549.
[29]Jones C,Allsopp L,Horlick J,et al.Subinhibitory concentration of kanamycin induces the Pseudomonas aeruginosa type VI secretion system[J].PloS one,2013,8(11):e81132.
[30]Martinez J L.Drug resistance:General principles of antibiotic resistance in bacteria[J].Drug Discov Today:Technol,2014,11:33-39.
[31]Wang S,Yang Y,Zhao Y,et al.Sub-MIC Tylosin Inhibits Streptococcus suis biofilm formation and results in differential protein expression[J].Front Microbiol,2016,7:384-392.
[32]Kwiecńskapiróg J,Skowron K,Zniszczol K,et al.The assessment of Proteus mirabilis susceptibility to ceftazidime and ciprofloxacin and the impact of these antibiotics at subinhibitory concentrations on Proteus mirabilis biofilms[J].Bio Med Res Int,2013,2013(6):930876.
[33]Nguyen U T,Harvey H,Hogan A J,et al.Role of PBPD1in stimulation of listeria monocytogenes biofilm formation by subminimal inhibitoryβ-lactam concentrations[J].Antimicrob Agents Chemother,2014,58(11):6508-6517.
[34]Haddadin R N,Saleh S,Adham I S,et al.The effect of subminimal inhibitory concentrations of antibiotics on virulence factors expressed by Staphylococcus aureus biofilms[J].J Appl Microbiol,2010,108(4):1281-1291.
[35]Balaji K,Thenmozhi R,Pandian S K.Effect of subinhibitory concentrations of fluoroquinolones on biofilm production by clinical isolates of Streptococcus pyogenes[J].Ind J Med Res,2013,137(5):963-971.
[36]Aka S T,Haji S H.Sub-MIC of antibiotics induced biofilm formation of Pseudomonas aeruginosa in the presence of chlorhexidine[J].Brazil J Microbiol:Publ Brazil Soci Microbiol,2015,46(1):149-154.
[37]De Souza Filho J A,Diniz C G,Barbosa N B,et al.Clinical microbiology:Morphological,biochemical,physiological and molecular aspects of the response of Fusobacterium nucleatum exposed to subinhibitory concentrations of antimicrobials[J].Anaerobe,2012,18(6):566-575.
[38]Maioli E,Marchese A,Roveta S,et al.In vitro activity of ceftibuten at sub-inhibitory concentrations in comparison with other antibiotics against respiratory and urinary tract pathogens[J].J Chemother,2014,19(2):152-160.
[39]Liu Z,Wang W,Zhu Y,et al.Antibiotics at subinhibitory concentrations improve the quorum sensing behavior of Chromobacterium violaceum[J].Fems Microbiol Lett,2013,341(1):37-44.
[40]Dorota W,Dorota T.Effect of sub-minimum inhibitory concentrations of ciprofloxacin,amikacin and colistin on biofilm formation and virulence factors of Escherichia coli planktonic and biofilm forms isolated from human urine[J].Lasers Electro-optics,2013,23(6):7471-7480.
[41]Ara J,Juhee A.Phenotypic and genotypic characterisation of multiple antibiotic-resistant Staphylococcus aureus exposed to subinhibitory levels of oxacillin and levofloxacin[J].Bmc Microbiol,2016,16(1):170-179.
[42]Kaplan J B,Jabbouri S,Sadovskaya I.Extracellular DNA-dependent biofilm formation by Staphylococcus epidermidis RP62A in response to subminimal inhibitory concentrations of antibiotics[J].Res Microbiol,2011,162(5):535-541.
[43]Husain F M,Ahmad I,Baig M H,et al.Broad-spectrum inhibition of AHL-regulated virulence factors and biofilms by sub-inhibitory concentrations of ceftazidime[J].RSCAdvan,2016,6(33):27952-27962.
[44]Starner T D,Shrout J D,Parsek M R,et al.Subinhibitory concentrations of azithromycin decrease nontypeable Haemophilus influenzae biofilm formation and Diminish established biofilms[J].Antimicrob Agents Chemother,2008,52(1):137-145.
[45]Roudashti S,Zeighami H,Mirshahabi H,et al.Synergistic activity of sub-inhibitory concentrations of curcumin with ceftazidime and ciprofloxacin against Pseudomonas aeruginosa quorum sensing related genes and virulence traits[J].World Jo Microbiol Biotechnol,2017,33(3):50-57.
[46]Li X Y,Xue F,Yang W W,et al.Effects of the subinhibitory concentration of levofloxacin promote virulence factor production of Pseudomonas aeruginosa[J].Chin J Clin Pharmacol,2013,5(163):355-357.
[47]Sophie H,Elisabeth K.Bacterial persisters:Formation,eradication,and experimental systems[J].Trends Microbiol,2014,22(7):417-424.
[48]Johnson P J T,Levin B R.Pharmacodynamics,population dynamics,and the evolution of persistence in Staphylococcus aureus[J].Plos Genetics,2013,9(1):e1003123.
[49]Dorr T,Lewis K,Vulic M.SOS Response induces persistence to fluoroquinolones in Escherichia coli[J].Plos Genetics,2009,5(12):e1000760.
[50]Hnternalization of Salmonella by macrophages induces formation of nonreplicating persisters[J].Science,2014,343(6167):204-208.
[51]Baharoglu Z,Mazel D.Vibrio cholerae triggers SOS and mutagenesis in response to a wide range of antibiotics:A route towards multiresistance[J].Antimicrob Agents Chemother,2011,55(5):2438-2441.
[52]Beaber J W,Hochhut B,Waldor M K.SOS response promotes horizontal dissemination of antibiotic resistance genes[J].Nature,2004,427(6969):72-74.
[53]Lopez E,Elez M,Matic I,et al.Antibiotic-mediated recombination:Ciprofloxacin stimulates SOS-independent recombination of divergent sequences in Escherichia coli[J].Molecul Microbiol,2007,64(1):83-93.
[54]Sandegren L,Dan I A.Bacterial gene amplification:Implications for the evolution of antibiotic resistance[J].Nat Rev Microbiol,2009,7(8):578-588.
[55]Gutierrez A,Laureti L,Crussard S,et al.Beta-lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity[J].Nat Communicat,2013,4:1610-1618.
[56]Nair C G,Chao C,Ryall B,et al.Sub-lethal concentrations of antibiotics increase mutation frequency in the cystic fibrosis pathogen Pseudomonas aeruginosa[J].Lett In Appl Microbiol,2013,56(2):149-154.
[57]Louise E,Liette E,Michael E.Potential impacts of aquatic pollutants:Sub-clinical antibiotic concentrations induce genome changes and promote antibiotic resistance[J].Front Microbiol,2015,6(803):803-812.
[58]Henderson-Begg S K,Livermore D M,Hall L M.Effect of subinhibitory concentrations of antibiotics on mutation frequency in Streptococcus pneumoniae[J].J Antimicrob Chemother,2006,57(5):849-854.
[59]Wang P,Zhang X N,Wang L,et al.Subinhibitory concentrations of ciprofloxacin induce SOS response and mutations of antibiotic resistance in bacteria[J].Ann Microbiol,2010,60(3):511-517.
[60]Roch M,Clataphylococcus aureus to subinhibitory concentrations ofβ-lactam antibiotics induces heterogeneous vancomycinintermediate Staphylococcus aureus[J].Antimicrob Agents Chemother,2014,58(9):5306-5314.
[61]Balaji K,Thenmozhi R,Pandian S K.Effect of subinhibitory concentrations of fluoroquinolones on biofilm production by clinical isolates of Streptococcus pyogenes[J].Ind J Med Res,2013,137(5):963-971.
[62]Shen S,Zhang T,Yuan Y,et al.Effects of cinnamaldehyde on Escherichia coli and Staphylococcus aureus membrane[J].Food Control,2015,47(47):196-202.
[63]Cortes P,Pinas G O A,Echenique J,et al.Subinhibitory concentrations of penicillin increase the mutation rate to optochin resistance in Streptococcus pneumoniae[J].JAntimicrob Chemother,2008,62(5):973-977.
[64]Goh E B,Yim G,Tsui W,et al.Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics[J].Proceed Nat Acad Scie USA,2002,99(26):17025.
[65]Garima K,Pathak R,Tandon R,et al.Differential expression of efflux pump genes of Mycobacterium tuberculosis in response to varied subinhibitory concentrations of antituberculosis agents[J].Tubercul,2015,95(2):155-161.
[66]Marti E,Huerta B,Rodríguezmozaz S,et al.Effects of subinhibitory ciprofloxacin concentrations on the abundance of qnrS and composition of bacterial communities from water supply reservoirs[J].Chemosphere,2016,161:470-474.
[67]Tattevin P,Basuino L,Chambers H F.Subinhibitory fluoroquinolone exposure selects for reduced beta-lactam susceptibility in methicillin-resistant Staphylococcus aureus and alterations in the SOS-mediated response[J].Res Microbiol,2009,160(3):187-92.
[68]Hua X T,Chen Q,Li X,et al.Global transcriptional response of Acinetobacter baumannii to a subinhibitory concentration of tigecycline[J].Int J Antimicrob Agents,2014,44(4):337-344.
[69]Cheng G Y,Hao H H,Dai M H,et al.Antibacterial action of quinolones:From target to network[J].Europ J Med Chem,2013,44(42):555-562.
[70]López E,Elez M,Matic I,et al.Antibiotic-mediated recombination:ciprofloxacin stimulates SOS-independent recombination of divergent sequences in Escherichia coli[J].Molecul Microbiol,2007,64(1):83-93.
[71]Jutkina J,Rutgersson C,Flach C F,et al.An assay for determining minimal concentrations of antibiotics that drive horizontal transfer of resistance[J].Sci Total Environ,2016,548-549:131-138.
[72]Brown S P,Cornforth D M,Mideo N.Evolution of virulence in opportunistic pathogens:generalism,plasticity,and control[J].Trends Microbiol,2012,20(7):336-342.
[73]Andrade J P,Farias L,Ferreira J F,et al.Sub-inhibitory concentration of piperacillin-tazobactam may be related to virulence properties of filamentous Escherichia coli[J].Curr Microbiol,2016,72(1):19-28.
[74]Sachdeva M,Leeds J A.Subinhibitory concentrations of LFF571 reduce toxin production by Clostridium difficile[J].Antimicrob Agents Chemother,2015,59(2):1252-1257.
[75]Ismaeel A Y,Senok A C,Bindayna K M,et al.Effect of antibiotic sub inhibitory concentration on cytolethal distending toxin production by Campylobacter jejuni[J].JInfect,2005,51(2):144-149.
[76]Haddadin R N,Saleh S,Aladham I S,et al.The effect of subminimal inhibitory concentrations of antibiotics on virulence factors expressed by Staphylococcus aureus biofilms[J].J Appl Microbiol,2010,108(4):1281-1291.
[77]Li D M,Renzoni A,Estoppey T,et al.Induction of fibronectin adhesins in quinolone-resistant Staphylococcus aureus by subinhibitory levels of ciprofloxacin or by sigma B transcription factor activity is mediated by two separate pathways[J].Antimicrob Agents Chemother,2005,49(3):916-924.
[78]Furneri P M,Garozzo A,Musumarra M P,et al.Effects on adhesiveness and hydrophobicity of sub-inhibitory concentrations of netilmicin[J].Int J Antimicrob Agents,2003,22(2):164-167.
[79]Gallardo-Moreno A M,Van Der Mei H C,Busscher H J,et al.Adhesion of Enterococcus faecalis 1131 grown under subinhibitory concentrations of ampicillin and vancomycin to a hydrophilic and a hydrophobic substratum[J].Fems Microbiol Lett,2001,203(1):75-79.
[80]Sinel C,Cacaci M,Meignen P,et al.Subinhibitory concentrations of ciprofloxacin enhance antimicrobial resistance and pathogenicity of Enterococcus faecium[J].Antimicrobial Agents Chemother,2017,61(5):AAC.02763-16.
[81]Rasigade J P,Moulay A,Lhoste Y,et al.Impact of subinhibitory antibiotics on fibronectin-mediated host cell adhesion and invasion by Staphylococcus aureus[J].BMCMicrobiol,2011,11(1):263-271.
[82]Vidya K C,Mallya P S,Rao P S.Inhibition of bacterial adhesion by subinhibitory concentrations of antibiotics[J].Ind J Med Microbiol,2005,23(2):102-105.
[83]Ogaard A R,Bj?ro K,Bukholm G,et al.Pseudomonas aeruginosa virulence factors:modifications by subinhibitory concentrations of carbenicillin or gentamicin[J].1986,94(2):63-68.
[84]Dal S M,Bovio C,Culici M,et al.Interference of subinhibitory concentrations of gatifloxacin on various determinants of bacterial virulence[J].J Chemother,2002,14(5):473-482.
[85]Pompilio A,Catavitello C,Picciani C,et al.Subinhibitory concentrations of moxifloxacin decrease adhesion and biofilm formation of Stenotrophomonas maltophilia from cystic fibrosis[J].J Med Microbiol,2010,59(1):76-81.
[86]Wojnicz D,Klak M,Adamski R,et al.Influence of subinhibitory concentrations of amikacin and ciprofloxacin on morphology and adherence ability of uropathogenic strains[J].Folia Microbiol,2007,52(4):429-436.
[87]Shen L,ShI Y,Zhang D,et al.Modulation of secreted virulence factor genes by subinhibitory concentrations of antibiotics in Pseudomonas aeruginosa[J].J Microbiol,2008,46(4):441-447.
[88]B raga P,Subinhibitory concentrations of rufloxacin on bacterial virulence factors[J].Antimicrob Agents Chemother,1999,43(5):1013-1019.
[89]Miyamoto K N,Monteiro K M,Caumo K D S,et al.Supporting data for comparative proteomic analysis of Listeria monocytogenes ATCC 7644 exposed to a sublethal concentration of nisin[J].2015,119:230-237.
[90]Tsai S H,Lai H C,Hu S T.Subinhibitory doses of Aaminoglycoside antibiotics induce changes in the phenotype of Mycobacterium abscessus[J].Antimicrob Agents Chemother,2015,59(10):6161-6169.
[91]Parul G,Sanjay C,Kusum H.Subinhibitory concentration of ciprofloxacin targets quorum sensing system of Pseudomonas aeruginosa causing inhibition of biofilm formation&reduction of virulence[J].Ind J Med Res,2016,143(5):643-651.
[92]Zhuang Y,Chen W,Yao F,et al.Short-term pretreatment of sub-inhibitory concentrations of gentamycin inhibits the swarming motility of Escherichia coli by down-regulating the succinate dehydrogenase gene[J].Cellul Physiol Biochem,2016,39(4):1307-1316.
[93]Lagrou K,Peetermans W E,Jorissen M,et al.Subinhibitory concentrations of erythromycin reduce pneumococcal adherence to respiratory epithelial cells in vitro[J].JAntimicrob Chemother,2000,46(5):717-723.
[94]Molinari G,Guzmán C A,Pesce A,et al.Inhibition of Pseudomonas aeruginosa virulence factors by subinhibitory antibiotics[J].J Antimicrobial Chemother,1993,31(5):681-688.
[95]Joo H S,Chan J L,Cheung G Y C,et al.Subinhibitory concentrations of protein synthesis-inhibiting antibiotics promote increased expression of the agr virulence regulator and production of phenol-soluble modulin cytolysins in community-associated methicillin-resistant Staphylococcus aureus[J].Antimicrob Agents Chemother,2010,54(11):4942-4944.
[96]Ohlsen K,Ziebuhr W,Koller K P,et al.Effects of subinhibitory concentrations of antibiotics on alphatoxin(hla)gene expression of methicillin-sensitive and methicillin-resistant Staphylococcus aureus isolates[J].Antimicrob Agents Chemother,1998,42(11):2817-2823.
[97]Gottschalk S,Ingmer H,Thomsen L E.The lysine-peptoid hybrid LP5 maintain activity under physiological conditions and affects virulence gene expression in Staphylococcus aureus[J].Peptides,2016,78:24-29.
[98]Ara J,Juhee A.Phenotypic and genotypic characterisation of multiple antibiotic-resistant Staphylococcus aureus exposed to subinhibitory levels of oxacillin and levofloxacin[J].BMCMicrobiol,2016,16(1):170-179.
[99]Lazaro-Diez M,Remuzgo-Martinez S,RodriguezMirones C,et al.Effects of subinhibitory concentrations of ceftaroline on methicillin-resistant Staphylococcus aureus(MRSA)biofilms[J].PloS one,2016,11(1):e0147569.
[100]Lück P C,Schmitt J W,Hengerer A,et al.Subinhibitory concentrations of antimicrobial agents reduce the uptake of Legionella pneumophila into Acanthamoeba castellanii and U937 Cells by altering the expression of virulenceassociated antigens[J].Antimicrob Agents Chemother,1998,42(11):2870-2876.
[101]Debbia E A,Maioli E,Roveta S,et al.Effects of rifaximin on bacterial virulence mechanisms at supra-and sub-inhibitory concentrations[J].J Chemother,2008,20(2):186-194.
[102]De Moura T M,Campos F S,Caierao J,et al.Influence of a subinhibitory concentration of vancomycin on the in vitro expression of virulence-related genes in the vancomycinresistant Enterococcus faecalis[J].Revista Da Socied Brasileira De Med Trop,2015,48(5):617-621.
[103]Haas B,Grenier D.Impact of sub-inhibitory concentrations of amoxicillin on streptococcus suis capsule gene expression and inflammatory potential[J].Pathog,2016,5(2):37-49.
[104]Otto M P,Martin E,Badiou C,et al.Effects of subinhibitory concentrations of antibiotics on virulence factor expression by community-acquired methicillin-resistant Staphylococcus aureus[J].J Antimicrob Chemother,2013,68(7):1524-1532.
[105]Wassermann T,Jorgensen K M,Ivanyshyn K,et al.The phenotypic evolution of Pseudomonas aeruginosa populations changes in the presence of subinhibitory concentrations of ciprofloxacin[J].Microbiol,2016,162(5):865-875.
[106]Yim G,Wang H H,Davies J.Antibiotics as signaling molecules[J].Philosoph Transact Royal Soci London,2007,362(1483):1195-1200.
[107]Popat R,Crusz S A,Messina M,et al.Quorum-sensing and cheating in bacterial biofilms[J].Proceed Biolog Sci,2012,279(1748):4765-4771.
[108]Goo E,An J H,Kang Y,et al.Control of bacterial metabolism by quorum sensing[J].Trends Microbiol,2015,23(9):567-576.
[109]Rutherford S T,Bassler B L.Bacterial quorum sensing:Its role in virulence and possibilities for its control[J].Cold Spring Harbor Perspectives Med,2012,2(11):705-709.