In vitro and in vivo activity of D-serine in combination with β-lactam antibiotics against methicillin-resistant Staphylococcus aureus
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摘要
As D-amino acids play important roles in the physiological metabolism of bacteria,combination of D-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate in vitro and in vivo activity of D-serine alone and in combination withβ-lactams against methicillin-resistant Staphylococcus aureus(MRSA) strains, and to explore the possible sensitization mechanisms. The activity of D-serine, β-lactams alone and in combinations was evaluated both in vitro by standard MICs, time–kill curves and checkerboard assays, and in vivo by murine systemic infection model as well as neutropenic thigh infection model. An in vitro synergistic effect was demonstrated with the combination of D-serine and β-lactams against MRSA standard and clinical strains.Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared toβ-lactam alone groups. Initial mechanism study suggested possible revision of D-alanine-D-alanine residue to D-alanine-D-serine in peptidoglycan by adding of D-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, D-serine had synergistic activity in combination with β-lactams against MRSA strains both in vitro and in vivo. Considering the relatively good safety of D-serine alone or in combination with β-lactams, D-serine is worth following up as new anti-MRSA infection strategies.
As D-amino acids play important roles in the physiological metabolism of bacteria,combination of D-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate in vitro and in vivo activity of D-serine alone and in combination with β-lactams against methicillin-resistant Staphylococcus aureus(MRSA) strains, and to explore the possible sensitization mechanisms. The activity of D-serine, β-lactams alone and in combinations was evaluated both in vitro by standard MICs, time–kill curves and checkerboard assays, and in vivo by murine systemic infection model as well as neutropenic thigh infection model. An in vitro synergistic effect was demonstrated with the combination of D-serine and β-lactams against MRSA standard and clinical strains.Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared to β-lactam alone groups. Initial mechanism study suggested possible revision of D-alanine-D-alanine residue to D-alanine-D-serine in peptidoglycan by adding of D-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, D-serine had synergistic activity in combination with β-lactams against MRSA strains both in vitro and in vivo. Considering the relatively good safety of D-serine alone or in combination with β-lactams, D-serine is worth following up as new anti-MRSA infection strategies.
As D-amino acids play important roles in the physiological metabolism of bacteria,combination of D-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate in vitro and in vivo activity of D-serine alone and in combination with β-lactams against methicillin-resistant Staphylococcus aureus(MRSA) strains, and to explore the possible sensitization mechanisms. The activity of D-serine, β-lactams alone and in combinations was evaluated both in vitro by standard MICs, time–kill curves and checkerboard assays, and in vivo by murine systemic infection model as well as neutropenic thigh infection model. An in vitro synergistic effect was demonstrated with the combination of D-serine and β-lactams against MRSA standard and clinical strains.Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared to β-lactam alone groups. Initial mechanism study suggested possible revision of D-alanine-D-alanine residue to D-alanine-D-serine in peptidoglycan by adding of D-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, D-serine had synergistic activity in combination with β-lactams against MRSA strains both in vitro and in vivo. Considering the relatively good safety of D-serine alone or in combination with β-lactams, D-serine is worth following up as new anti-MRSA infection strategies.
引文
1.Talan DA,Krishnadasan A,Gorwitz RJ,Fosheim GE,Limbago B,Albrecht V,et al.Comparison of Staphylococcus aureus from skin and soft-tissue infections in US emergency department patients,2004 and2008.Clin Infect Dis 2011;53:144-9.
2.Tong SY,Davis JS,Eichenberger E,Holland TL,Fowler VG Jr.Staphylococcus aureus infections:epidemiology,pathophysiology,clinical manifestations,and management.Clin Microbiol Rev2015;28:603-61.
3.Klevens RM,Morrison MA,Nadle J,Petit S,Gershman K,Ray S,et al.Invasive methicillin-resistant Staphylococcus aureus infections in the United States.JAMA 2007;298:1763-71.
4.Dantes R,Mu Y,Belflower R,Aragon D,Dumyati G,Harrison LH,et al.National burden of invasive methicillin-resistant Staphylococcus aureus infections,United States,2011.JAMA Intern Med2013;173:1970-8.
5.Nguyen DB,Lessa FC,Belflower R,Mu Y,Wise M,Nadle J,et al.Invasive methicillin-resistant Staphylococcus aureus infections among patients on chronic dialysis in the United States,2005-2011.Clin Infect Dis 2013;57:1393-400.
6.Chaudhary AS.A review of global initiatives to fight antibiotic resistance and recent antibiotics'discovery.Acta Pharm Sin B2016;6:552-6.
7.Cava F,de Pedro MA,Lam H,Davis BM,Waldor MK.Distinct pathways for modification of the bacterial cell wall by non-canonical D-amino acids.EMBO J 2011;30:3442-53.
8.Cava F,Lam H,de Pedro MA,Waldor MK.Emerging knowledge of regulatory roles of D-amino acids in bacteria.Cell Mol Life Sci2011;68:817-31.
9.Radkov AD,Hsu YP,Booher G,Van Nieuwenhze MS.Imaging Bacterial Cell Wall Biosynthesis.Annu Rev Biochem 2018;87:991-1014.
10.Caparrós M,Pisabarro AG,de Pedro MA.Effect of D-amino acids on structure and synthesis of peptidoglycan in Escherichia coli.JBacteriol 1992;174:5549-59.
11.Lam H,Oh DC,Cava F,Takacs CN,Clardy J,de Pedro MA,et al.D-amino acids govern stationary phase cell wall remodeling in bacteria.Science 2009;325:1552-5.
12.Kolodkin-Gal I,Romero D,Cao S,Clardy J,Kolter R,Losick R.D-amino acids trigger biofilm disassembly.Science 2010;328:627-9.
13.Hochbaum AI,Kolodkin-Gal I,Foulston L,Kolter R,Aizenberg J,Losick R.Inhibitory effects of D-amino acids on Staphylococcus aureus biofilm development.J Bacteriol 2011;193:5616-22.
14.Ramón-Peréz ML,Diaz-Cedillo F,Ibarra JA,Torales-Carde?a A,Rodríguez-Martínez S,Jan-Roblero J.D-amino acids inhibit biofilm formation in Staphylococcus epidermidis strains from ocular infections.J Med Microbiol 2014;63:1369-76.
15.Yang H,Wang M,Yu J,Wei H.Aspartate inhibits Staphylococcus aureus biofilm formation.FEMS Microbiol Lett 2015;362:1-7.
16.Sanchez Jr CJ,Akers KS,Romano DR,Woodbury RL,Hardy SK,Murray CK,et al.D-amino acids enhance the activity of antimicrobials against biofilms of clinical wound isolates of Staphylococcus aureus and Pseudomonas aeruginosa.Antimicrob Agents Chemother2014;58:4353-61.
17.She P,Chen L,Liu H,Zou Y,Luo Z,Koronfel A,et al.The effects of D-tyrosine combined with amikacin on the biofilms of Pseudomonas aeruginosa.Microb Pathog 2015;86:38-44.
18.Tong Z,Zhang L,Ling J,Jian Y,Huang L,Deng D.An in vitro study on the effect of free amino acids alone or in combination with nisin on biofilms as well as on planktonic bacteria of Streptococcus mutans.PLoS One 2014;9:e99513.
19.De Jonge BL,Gage D,Xu N.The carboxyl terminus of peptidoglycan stem peptides is a determinant for methicillin resistance in Staphylococcus aureus.Antimicrob Agents Chemother 2002;46:3151-5.
20.Enright MC,Day NP,Davies CE,Peacock SJ,Spratt BG.Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus.J Clin Microbiol 2000;38:1008-15.
21.Koreen L,Ramaswamy SV,Graviss EA,Naidich S,Musser JM,Kreiswirth BN.spa typing method for discriminating among Staphylococcus aureus isolates:implications for use of a single marker to detect genetic micro-and macrovariation.J Clin Microbiol2004;42:792-9.
22.?https://clsi.org/?.Clinical and Laboratory Standards Institute.Performance Standard for Antimicrobial Susceptibility Testing;Twenty-Fifth Informational Supplement.CLSI document M100-S25.Clinical and Laboratory Standards Institute,950 West Valley Road,Suite 2500,Wayne,Pennsylvania 19087 USA,2015.
23.Verma P.Methods for determining bactericidal activity and antimicrobial interactions synergy testing,time-kill curves,and population analysis.In:Schwalbe R,Steele-Moore L,Goodwin AC,editors.Antimicrobial Susceptibility Testing Protoccols.Boca Raton:CRCPress;2007.p.275-98.
24.Lu X,Yang X,Li X,Lu Y,Ren Z,Zhao L,et al.In vitro activity of sodium new houttuyfonate alone and in combination with oxacillin or netilmicin against methicillin-resistant Staphylococcus aureus.PLoSOne 2013;8:e68053.
25.Zuluaga AF,Salazar BE,Rodriguez CA,Zapata AX,Agudelo M,Vesga O.Neutropenia induced in outbred mice by a simplified lowdose cyclophosphamide regimen:characterization and applicability to diverse experimental models of infectious diseases.BMC Infect Dis2006;6:55.
26.Labrou M,Michail G,Ntokou E,Pittaras TE,Pournaras S,Tsakris A.Activity of oxacillin versus that of vancomycin against oxacillinsusceptible mecA-positive Staphylococcus aureus clinical isolates evaluated by population analyses,time-kill assays,and a murine thigh infection model.Antimicrob Agents Chemother 2012;56:3388-91.
27.Dandekar PK,Tessier PR,Williams P,Nightingale CH,Nicolau DP.Pharmacodynamic profile of daptomycin against Enterococcus species and methicillin-resistant Staphylococcus aureus in a murine thigh infection model.J Antimicrob Chemother 2003;52:405-11.
28.Sugihara K,Sugihara C,Matsushita Y,Yamamura N,Uemori M,Tokumitsu A,et al.In vivo pharmacodynamic activity of tomopenem(formerly CS-023)against Pseudomonas aeruginosa and methicillinresistant Staphylococcus aureus in a murine thigh infection model.Antimicrob Agents Chemother 2010;54:5298-302.
29.Janardhanan J,Meisel JE,Ding D,Schroeder VA,Wolter WR,Mobashery S,et al.In vitro and in vivo synergy of the oxadiazole class of antibacterials withβ-lactams.Antimicrob Agents Chemother2016;60:5581-8.
30.Wang W,Liu C,Zhu N,Lin Y,Jiang J,Wang Y,et al.Identification of anti-Gram-negative bacteria agents targeting the interaction between ribosomal proteins L12 and L10.Acta Pharm Sin B 2018;8:772-83.
31.Wang L,Yang R,Yuan B,Liu Y,Liu C.The antiviral and antimicrobial activities of licorice,a widely-used Chinese herb.Acta Pharm Sin B 2015;5:310-5.
32.Jenkins RE,Cooper R.Synergy between oxacillin and manuka honey sensitizes methicillin-resistant Staphylococcus aureus to oxacillin.JAntimicrob Chemother 2012;67:1405-7.
33.Gaur R,Gupta VK,Singh P,Pal A,Darokar MP,Bhakuni RS.Drug resistance reversal potential of isoliquiritigenin and liquiritigenin isolated from Glycyrrhiza glabra against methicillin-resistant Staphylococcus aureus(MRSA).Phytother Res 2016;30:1708-15.
34.Lahmar A,Bedoui A,Mokdad-Bzeouich I,Dhaouifi Z,Kalboussi Z,Cheraif I,et al.Reversal of resistance in bacteria underlies synergistic effect of essential oils with conventional antibiotics.Microb Pathog2017;106:50-9.
35.Biedenbach DJ,Alm RA,Lahiri SD,Reiszner E,Hoban DJ,Sahm DF,et al.In vitro activity of ceftaroline against Staphylococcus aureus isolated in 2012 from Asia-Pacific countries as part of the AWAREsurveillance program.Antimicrob Agents Chemother 2015;60:343-7.
36.Biedenbach DJ,Hoban DJ,Reiszner E,Lahiri SD,Alm RA,Sahm DF,et al.In vitro activity of ceftaroline against Staphylococcus aureus isolates collected in 2012 from Latin American countries as part of the AWARE surveillance program.Antimicrob Agents Chemother2015;59:7873-7.
37.Guignard B,Entenza JM,Moreillon P.β-Lactams against methicillinresistant Staphylococcus aureus.Curr Opin Pharmacol 2005;5:479-89.
38.Katayama Y,Ito T,Hiramatsu K.A new class of genetic element,Staphylococcus cassette chromosome mec,encodes methicillin resistance in Staphylococcus aureus.Antimicrob Agents Chemother2000;44:1549-55.
39.Chambers HF,Hartman BJ,Tomasz A.Increased amounts of a novel penicillin-binding protein in a strain of methicillin-resistant Staphylococcus aureus exposed to nafcillin.J Clin Invest 1985;76:325-31.
40.Thorsing M,Klitgaard JK,Atilano ML,Skov MN,Kolmos HJ,Filipe SR,et al.Thioridazine induces major changes in global gene expression and cell wall composition in methicillin-resistant Staphylococcus aureus USA300.PLoS One 2013;8:e64518.
41.Chambers HF,Sachdeva M.Binding ofβ-lactam antibiotics to penicillin-binding proteins in methicillin-resistant Staphylococcus aureus.J Infect Dis 1990;161:1170-6.
42.Sieradzki K,Tomasz A.Suppression ofβ-lactam antibiotic resistance in a methicillin-resistant Staphylococcus aureus through synergic action of early cell wall inhibitors and some other antibiotics.JAntimicrob Chemother 1997;39 Suppl A:47-51.
43.Hamilton SM,Alexander JAN,Choo EJ,Basuino L,da Costa TM,Severin A,et al.High-level resistance of Staphylococcus aureus toβ-lactam antibiotics mediated by penicillin-binding protein 4(PBP4).Antimicrob Agents Chemother 2017;61:e02727-16.
44.Chatterjee SS,Chen L,Gilbert A,da Costa TM,Nair V,Datta SK,et al.PBP4 mediatesβ-lactam resistance by altered function.Antimicrob Agents Chemother 2017;61:e00932-17.
45.Williams RE,Lock EA.Sodium benzoate attenuates D-serine induced nephrotoxicity in the rat.Toxicology 2005;207:35-48.
46.Chung SP,Sogabe K,Park HK,Song Y,Ono K,Abou El-Magd RM,et al.Potential cytotoxic effect of hydroxypyruvate produced from D-serine by astroglial D-amino acid oxidase.J Biochem 2010;148:743-753.
47.Ferraris D,Duvall B,Ko YS,Thomas AG,Rojas C,Majer P,et al.Synthesis and biological evaluation of D-amino acid oxidase inhibitors.J Med Chem 2008;51:3357-9.
2.Tong SY,Davis JS,Eichenberger E,Holland TL,Fowler VG Jr.Staphylococcus aureus infections:epidemiology,pathophysiology,clinical manifestations,and management.Clin Microbiol Rev2015;28:603-61.
3.Klevens RM,Morrison MA,Nadle J,Petit S,Gershman K,Ray S,et al.Invasive methicillin-resistant Staphylococcus aureus infections in the United States.JAMA 2007;298:1763-71.
4.Dantes R,Mu Y,Belflower R,Aragon D,Dumyati G,Harrison LH,et al.National burden of invasive methicillin-resistant Staphylococcus aureus infections,United States,2011.JAMA Intern Med2013;173:1970-8.
5.Nguyen DB,Lessa FC,Belflower R,Mu Y,Wise M,Nadle J,et al.Invasive methicillin-resistant Staphylococcus aureus infections among patients on chronic dialysis in the United States,2005-2011.Clin Infect Dis 2013;57:1393-400.
6.Chaudhary AS.A review of global initiatives to fight antibiotic resistance and recent antibiotics'discovery.Acta Pharm Sin B2016;6:552-6.
7.Cava F,de Pedro MA,Lam H,Davis BM,Waldor MK.Distinct pathways for modification of the bacterial cell wall by non-canonical D-amino acids.EMBO J 2011;30:3442-53.
8.Cava F,Lam H,de Pedro MA,Waldor MK.Emerging knowledge of regulatory roles of D-amino acids in bacteria.Cell Mol Life Sci2011;68:817-31.
9.Radkov AD,Hsu YP,Booher G,Van Nieuwenhze MS.Imaging Bacterial Cell Wall Biosynthesis.Annu Rev Biochem 2018;87:991-1014.
10.Caparrós M,Pisabarro AG,de Pedro MA.Effect of D-amino acids on structure and synthesis of peptidoglycan in Escherichia coli.JBacteriol 1992;174:5549-59.
11.Lam H,Oh DC,Cava F,Takacs CN,Clardy J,de Pedro MA,et al.D-amino acids govern stationary phase cell wall remodeling in bacteria.Science 2009;325:1552-5.
12.Kolodkin-Gal I,Romero D,Cao S,Clardy J,Kolter R,Losick R.D-amino acids trigger biofilm disassembly.Science 2010;328:627-9.
13.Hochbaum AI,Kolodkin-Gal I,Foulston L,Kolter R,Aizenberg J,Losick R.Inhibitory effects of D-amino acids on Staphylococcus aureus biofilm development.J Bacteriol 2011;193:5616-22.
14.Ramón-Peréz ML,Diaz-Cedillo F,Ibarra JA,Torales-Carde?a A,Rodríguez-Martínez S,Jan-Roblero J.D-amino acids inhibit biofilm formation in Staphylococcus epidermidis strains from ocular infections.J Med Microbiol 2014;63:1369-76.
15.Yang H,Wang M,Yu J,Wei H.Aspartate inhibits Staphylococcus aureus biofilm formation.FEMS Microbiol Lett 2015;362:1-7.
16.Sanchez Jr CJ,Akers KS,Romano DR,Woodbury RL,Hardy SK,Murray CK,et al.D-amino acids enhance the activity of antimicrobials against biofilms of clinical wound isolates of Staphylococcus aureus and Pseudomonas aeruginosa.Antimicrob Agents Chemother2014;58:4353-61.
17.She P,Chen L,Liu H,Zou Y,Luo Z,Koronfel A,et al.The effects of D-tyrosine combined with amikacin on the biofilms of Pseudomonas aeruginosa.Microb Pathog 2015;86:38-44.
18.Tong Z,Zhang L,Ling J,Jian Y,Huang L,Deng D.An in vitro study on the effect of free amino acids alone or in combination with nisin on biofilms as well as on planktonic bacteria of Streptococcus mutans.PLoS One 2014;9:e99513.
19.De Jonge BL,Gage D,Xu N.The carboxyl terminus of peptidoglycan stem peptides is a determinant for methicillin resistance in Staphylococcus aureus.Antimicrob Agents Chemother 2002;46:3151-5.
20.Enright MC,Day NP,Davies CE,Peacock SJ,Spratt BG.Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus.J Clin Microbiol 2000;38:1008-15.
21.Koreen L,Ramaswamy SV,Graviss EA,Naidich S,Musser JM,Kreiswirth BN.spa typing method for discriminating among Staphylococcus aureus isolates:implications for use of a single marker to detect genetic micro-and macrovariation.J Clin Microbiol2004;42:792-9.
22.?https://clsi.org/?.Clinical and Laboratory Standards Institute.Performance Standard for Antimicrobial Susceptibility Testing;Twenty-Fifth Informational Supplement.CLSI document M100-S25.Clinical and Laboratory Standards Institute,950 West Valley Road,Suite 2500,Wayne,Pennsylvania 19087 USA,2015.
23.Verma P.Methods for determining bactericidal activity and antimicrobial interactions synergy testing,time-kill curves,and population analysis.In:Schwalbe R,Steele-Moore L,Goodwin AC,editors.Antimicrobial Susceptibility Testing Protoccols.Boca Raton:CRCPress;2007.p.275-98.
24.Lu X,Yang X,Li X,Lu Y,Ren Z,Zhao L,et al.In vitro activity of sodium new houttuyfonate alone and in combination with oxacillin or netilmicin against methicillin-resistant Staphylococcus aureus.PLoSOne 2013;8:e68053.
25.Zuluaga AF,Salazar BE,Rodriguez CA,Zapata AX,Agudelo M,Vesga O.Neutropenia induced in outbred mice by a simplified lowdose cyclophosphamide regimen:characterization and applicability to diverse experimental models of infectious diseases.BMC Infect Dis2006;6:55.
26.Labrou M,Michail G,Ntokou E,Pittaras TE,Pournaras S,Tsakris A.Activity of oxacillin versus that of vancomycin against oxacillinsusceptible mecA-positive Staphylococcus aureus clinical isolates evaluated by population analyses,time-kill assays,and a murine thigh infection model.Antimicrob Agents Chemother 2012;56:3388-91.
27.Dandekar PK,Tessier PR,Williams P,Nightingale CH,Nicolau DP.Pharmacodynamic profile of daptomycin against Enterococcus species and methicillin-resistant Staphylococcus aureus in a murine thigh infection model.J Antimicrob Chemother 2003;52:405-11.
28.Sugihara K,Sugihara C,Matsushita Y,Yamamura N,Uemori M,Tokumitsu A,et al.In vivo pharmacodynamic activity of tomopenem(formerly CS-023)against Pseudomonas aeruginosa and methicillinresistant Staphylococcus aureus in a murine thigh infection model.Antimicrob Agents Chemother 2010;54:5298-302.
29.Janardhanan J,Meisel JE,Ding D,Schroeder VA,Wolter WR,Mobashery S,et al.In vitro and in vivo synergy of the oxadiazole class of antibacterials withβ-lactams.Antimicrob Agents Chemother2016;60:5581-8.
30.Wang W,Liu C,Zhu N,Lin Y,Jiang J,Wang Y,et al.Identification of anti-Gram-negative bacteria agents targeting the interaction between ribosomal proteins L12 and L10.Acta Pharm Sin B 2018;8:772-83.
31.Wang L,Yang R,Yuan B,Liu Y,Liu C.The antiviral and antimicrobial activities of licorice,a widely-used Chinese herb.Acta Pharm Sin B 2015;5:310-5.
32.Jenkins RE,Cooper R.Synergy between oxacillin and manuka honey sensitizes methicillin-resistant Staphylococcus aureus to oxacillin.JAntimicrob Chemother 2012;67:1405-7.
33.Gaur R,Gupta VK,Singh P,Pal A,Darokar MP,Bhakuni RS.Drug resistance reversal potential of isoliquiritigenin and liquiritigenin isolated from Glycyrrhiza glabra against methicillin-resistant Staphylococcus aureus(MRSA).Phytother Res 2016;30:1708-15.
34.Lahmar A,Bedoui A,Mokdad-Bzeouich I,Dhaouifi Z,Kalboussi Z,Cheraif I,et al.Reversal of resistance in bacteria underlies synergistic effect of essential oils with conventional antibiotics.Microb Pathog2017;106:50-9.
35.Biedenbach DJ,Alm RA,Lahiri SD,Reiszner E,Hoban DJ,Sahm DF,et al.In vitro activity of ceftaroline against Staphylococcus aureus isolated in 2012 from Asia-Pacific countries as part of the AWAREsurveillance program.Antimicrob Agents Chemother 2015;60:343-7.
36.Biedenbach DJ,Hoban DJ,Reiszner E,Lahiri SD,Alm RA,Sahm DF,et al.In vitro activity of ceftaroline against Staphylococcus aureus isolates collected in 2012 from Latin American countries as part of the AWARE surveillance program.Antimicrob Agents Chemother2015;59:7873-7.
37.Guignard B,Entenza JM,Moreillon P.β-Lactams against methicillinresistant Staphylococcus aureus.Curr Opin Pharmacol 2005;5:479-89.
38.Katayama Y,Ito T,Hiramatsu K.A new class of genetic element,Staphylococcus cassette chromosome mec,encodes methicillin resistance in Staphylococcus aureus.Antimicrob Agents Chemother2000;44:1549-55.
39.Chambers HF,Hartman BJ,Tomasz A.Increased amounts of a novel penicillin-binding protein in a strain of methicillin-resistant Staphylococcus aureus exposed to nafcillin.J Clin Invest 1985;76:325-31.
40.Thorsing M,Klitgaard JK,Atilano ML,Skov MN,Kolmos HJ,Filipe SR,et al.Thioridazine induces major changes in global gene expression and cell wall composition in methicillin-resistant Staphylococcus aureus USA300.PLoS One 2013;8:e64518.
41.Chambers HF,Sachdeva M.Binding ofβ-lactam antibiotics to penicillin-binding proteins in methicillin-resistant Staphylococcus aureus.J Infect Dis 1990;161:1170-6.
42.Sieradzki K,Tomasz A.Suppression ofβ-lactam antibiotic resistance in a methicillin-resistant Staphylococcus aureus through synergic action of early cell wall inhibitors and some other antibiotics.JAntimicrob Chemother 1997;39 Suppl A:47-51.
43.Hamilton SM,Alexander JAN,Choo EJ,Basuino L,da Costa TM,Severin A,et al.High-level resistance of Staphylococcus aureus toβ-lactam antibiotics mediated by penicillin-binding protein 4(PBP4).Antimicrob Agents Chemother 2017;61:e02727-16.
44.Chatterjee SS,Chen L,Gilbert A,da Costa TM,Nair V,Datta SK,et al.PBP4 mediatesβ-lactam resistance by altered function.Antimicrob Agents Chemother 2017;61:e00932-17.
45.Williams RE,Lock EA.Sodium benzoate attenuates D-serine induced nephrotoxicity in the rat.Toxicology 2005;207:35-48.
46.Chung SP,Sogabe K,Park HK,Song Y,Ono K,Abou El-Magd RM,et al.Potential cytotoxic effect of hydroxypyruvate produced from D-serine by astroglial D-amino acid oxidase.J Biochem 2010;148:743-753.
47.Ferraris D,Duvall B,Ko YS,Thomas AG,Rojas C,Majer P,et al.Synthesis and biological evaluation of D-amino acid oxidase inhibitors.J Med Chem 2008;51:3357-9.