Effect of Short-Term Antimicrobial Therapy on the Tolerance and Antibiotic Resistance of Multidrug-Resistant Staphylococcus capitis

Xiao Yu,1,* Beiwen Zheng,1,* Feng Xiao,2 Ye Jin,1 Lihua Guo,1 Hao Xu,1 Qixia Luo,1 Yonghong Xiao1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infect...

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Main Authors: Yu X, Zheng B, Xiao F, Jin Y, Guo L, Xu H, Luo Q, Xiao Y
Format: Article
Language:English
Published: Dove Medical Press 2020-06-01
Series:Infection and Drug Resistance
Subjects:
Online Access:https://www.dovepress.com/effect-of-short-term-antimicrobial-therapy-on-the-tolerance-and-antibi-peer-reviewed-article-IDR
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spelling doaj-b7e7a1de1bc2407eafe4617238453c082020-11-25T02:40:47ZengDove Medical PressInfection and Drug Resistance1178-69732020-06-01Volume 132017202654937Effect of Short-Term Antimicrobial Therapy on the Tolerance and Antibiotic Resistance of Multidrug-Resistant Staphylococcus capitisYu XZheng BXiao FJin YGuo LXu HLuo QXiao YXiao Yu,1,* Beiwen Zheng,1,* Feng Xiao,2 Ye Jin,1 Lihua Guo,1 Hao Xu,1 Qixia Luo,1 Yonghong Xiao1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Neurosurgery Department, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghong Xiao Email xiaoyonghong@zju.edu.cnBackground: Bacteria undergo adaptive mutation in the host. However, the specific effect of antimicrobial use on bacterial evolution and genome mutations related to bacterial survival within a patient is unclear.Materials and Methods: Three S. capitis strains were sequentially isolated from cerebrospinal fluid of a clinical inpatient. Antimicrobial susceptibility, growth rate, biofilm formation and whole blood survival of these strains were measured. Relative fitness was calculated. The virulence was examined in the Galleria mellonella model. Whole-genome sequencing and in silico analysis were performed to explore the genetic mechanisms of the changes in antimicrobial resistance phenotype. Hypothetical proteins are cloned, expressed and characterized by detection the susceptibility to gentamycin.Results: The first isolate was susceptible to rifampin (MIC=0.25 μg/mL), resistant to gentamicin (MIC=16 μg/mL), while the later two isolates were resistant to rifampin (MIC > 64 μg/mL), susceptible to gentamicin (MIC=4 μg/mL). For the latter two strains, compared to the first, frameshift mutation in a hypothetical protein encoding gene and base substitutions (in genes saeR, moaA and rpoB) were discovered. The mutation of rpoB gene caused rifampicin resistance. Mutations in saeR, moaA and hypothetical gene are associated with changes in other biological traits. Amino acid sequence-based structure and function identification of the hypothetical protein indicated that a mutation in the encoding gene might be associated with altered aminoglycoside susceptibility. Growth curve showed that the later two isolates grew faster than the first isolate with a positive fitness advantage of 13.5%, and 14.8%, accordingly. Biofilm form ability and whole blood survival of the derivative mutants were also enhanced. No significant differences of virulence in the G. mellonella model were observed.Conclusion: We report here for the first time that short-term clinical antibiotic use was associated with resistance mutations, collateral sensitivity, and positive in vivo fitness advantages to S. capitis during infection.Keywords: resistance, mutations, collateral sensitivity, adaptive enhancement, selective pressurehttps://www.dovepress.com/effect-of-short-term-antimicrobial-therapy-on-the-tolerance-and-antibi-peer-reviewed-article-IDRresistancemutationscollateral sensitivityadaptive enhancementselective pressure
collection DOAJ
language English
format Article
sources DOAJ
author Yu X
Zheng B
Xiao F
Jin Y
Guo L
Xu H
Luo Q
Xiao Y
spellingShingle Yu X
Zheng B
Xiao F
Jin Y
Guo L
Xu H
Luo Q
Xiao Y
Effect of Short-Term Antimicrobial Therapy on the Tolerance and Antibiotic Resistance of Multidrug-Resistant Staphylococcus capitis
Infection and Drug Resistance
resistance
mutations
collateral sensitivity
adaptive enhancement
selective pressure
author_facet Yu X
Zheng B
Xiao F
Jin Y
Guo L
Xu H
Luo Q
Xiao Y
author_sort Yu X
title Effect of Short-Term Antimicrobial Therapy on the Tolerance and Antibiotic Resistance of Multidrug-Resistant Staphylococcus capitis
title_short Effect of Short-Term Antimicrobial Therapy on the Tolerance and Antibiotic Resistance of Multidrug-Resistant Staphylococcus capitis
title_full Effect of Short-Term Antimicrobial Therapy on the Tolerance and Antibiotic Resistance of Multidrug-Resistant Staphylococcus capitis
title_fullStr Effect of Short-Term Antimicrobial Therapy on the Tolerance and Antibiotic Resistance of Multidrug-Resistant Staphylococcus capitis
title_full_unstemmed Effect of Short-Term Antimicrobial Therapy on the Tolerance and Antibiotic Resistance of Multidrug-Resistant Staphylococcus capitis
title_sort effect of short-term antimicrobial therapy on the tolerance and antibiotic resistance of multidrug-resistant staphylococcus capitis
publisher Dove Medical Press
series Infection and Drug Resistance
issn 1178-6973
publishDate 2020-06-01
description Xiao Yu,1,* Beiwen Zheng,1,* Feng Xiao,2 Ye Jin,1 Lihua Guo,1 Hao Xu,1 Qixia Luo,1 Yonghong Xiao1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Neurosurgery Department, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghong Xiao Email xiaoyonghong@zju.edu.cnBackground: Bacteria undergo adaptive mutation in the host. However, the specific effect of antimicrobial use on bacterial evolution and genome mutations related to bacterial survival within a patient is unclear.Materials and Methods: Three S. capitis strains were sequentially isolated from cerebrospinal fluid of a clinical inpatient. Antimicrobial susceptibility, growth rate, biofilm formation and whole blood survival of these strains were measured. Relative fitness was calculated. The virulence was examined in the Galleria mellonella model. Whole-genome sequencing and in silico analysis were performed to explore the genetic mechanisms of the changes in antimicrobial resistance phenotype. Hypothetical proteins are cloned, expressed and characterized by detection the susceptibility to gentamycin.Results: The first isolate was susceptible to rifampin (MIC=0.25 μg/mL), resistant to gentamicin (MIC=16 μg/mL), while the later two isolates were resistant to rifampin (MIC > 64 μg/mL), susceptible to gentamicin (MIC=4 μg/mL). For the latter two strains, compared to the first, frameshift mutation in a hypothetical protein encoding gene and base substitutions (in genes saeR, moaA and rpoB) were discovered. The mutation of rpoB gene caused rifampicin resistance. Mutations in saeR, moaA and hypothetical gene are associated with changes in other biological traits. Amino acid sequence-based structure and function identification of the hypothetical protein indicated that a mutation in the encoding gene might be associated with altered aminoglycoside susceptibility. Growth curve showed that the later two isolates grew faster than the first isolate with a positive fitness advantage of 13.5%, and 14.8%, accordingly. Biofilm form ability and whole blood survival of the derivative mutants were also enhanced. No significant differences of virulence in the G. mellonella model were observed.Conclusion: We report here for the first time that short-term clinical antibiotic use was associated with resistance mutations, collateral sensitivity, and positive in vivo fitness advantages to S. capitis during infection.Keywords: resistance, mutations, collateral sensitivity, adaptive enhancement, selective pressure
topic resistance
mutations
collateral sensitivity
adaptive enhancement
selective pressure
url https://www.dovepress.com/effect-of-short-term-antimicrobial-therapy-on-the-tolerance-and-antibi-peer-reviewed-article-IDR
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