Epistasis analysis uncovers hidden antibiotic resistance-associated fitness costs hampering the evolution of MRSA

Genome Biology
Maho YokoyamaRuth C Massey

Abstract

Fitness costs imposed on bacteria by antibiotic resistance mechanisms are believed to hamper their dissemination. The scale of these costs is highly variable. Some, including resistance of Staphylococcus aureus to the clinically important antibiotic mupirocin, have been reported as being cost-free, which suggests that there are few barriers preventing their global spread. However, this is not supported by surveillance data in healthy communities, which indicate that this resistance mechanism is relatively unsuccessful. Epistasis analysis on two collections of MRSA provides an explanation for this discord, where the mupirocin resistance-conferring mutation of the ileS gene appears to affect the levels of toxins produced by S. aureus when combined with specific polymorphisms at other loci. Proteomic analysis demonstrates that the activity of the secretory apparatus of the PSM family of toxins is affected by mupirocin resistance. As an energetically costly activity, this reduction in toxicity masks the fitness costs associated with this resistance mutation, a cost that becomes apparent when toxin production becomes necessary. This hidden fitness cost provides a likely explanation for why this mupirocin-resistance mechanism is not ...Continue Reading

References

Aug 1, 1980·International Journal of Cancer. Journal International Du Cancer·S TsuchiyaK Tada
Oct 23, 1997·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·J S Bertino
Nov 16, 2002·Analytical Chemistry·Michael J MacCossJohn R Yates
May 3, 2003·The Journal of Clinical Investigation·Franklin D Lowy
Nov 29, 2005·The Lancet Infectious Diseases·Heiman F L WertheimJan L Nouwen
Jun 1, 2006·The American Journal of Medicine·Fred C Tenover
May 28, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Rachel J Gordon, Franklin D Lowy
Aug 14, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jean B PatelJohn A Jernigan
Jan 15, 2010·The ISME Journal·James CollinsRuth C Massey
Mar 2, 2010·Nature Reviews. Microbiology·Christopher M ThomasThomas J Simpson
Nov 23, 2011·Antimicrobial Agents and Chemotherapy·Swantje ReissSusanne Engelmann
Nov 26, 2011·The Lancet Infectious Diseases·Andrew E Simor
Jan 19, 2012·Antimicrobial Agents and Chemotherapy·Christine SeahRoberto G Melano
Apr 18, 2012·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Anton BankevichPavel A Pevzner
Jun 6, 2012·Methods in Molecular Biology·Loïc Dayon, Jean-Charles Sanchez
Feb 12, 2013·Nature Medicine·Som S ChatterjeeMichael Otto
Sep 3, 2013·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Jean-Philippe Rasigade, François Vandenesch
Oct 23, 2013·The Journal of Hospital Infection·D J Hetem, M J M Bonten
Oct 24, 2013·Current Infectious Disease Reports·C L AbadN Safdar
Apr 11, 2014·Genome Research·Maisem LaabeiRuth C Massey
Apr 11, 2015·Evolutionary Applications·Anita H MelnykRees Kassen
May 10, 2015·The Journal of Antimicrobial Chemotherapy·Kinga I Stanczak-MrozekJodi A Lindsay
Apr 19, 2017·PLoS Biology·Jorge Moura de SousaIsabel Gordo
Jun 9, 2017·Clinical Microbiology Reviews·Deborah A WilliamsonBenjamin P Howden
Aug 9, 2017·Nature Microbiology·Mario ReckerRuth C Massey

❮ Previous
Next ❯

Citations

Jan 9, 2020·Microbial Genomics·Stefano G GiulieriDeborah A Williamson
Jun 24, 2020·Infection and Immunity·Seána DugganRuth C Massey
May 7, 2019·Frontiers in Microbiology·Mengdi RongXiaoqing He
Mar 20, 2019·Nature Ecology & Evolution·Michael A BrockhurstCraig Maclean
Mar 25, 2019·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·Emily C DeasyAnna C Shore
Jan 9, 2021·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Abdelaziz TouatiAssia Mairi
Sep 8, 2019·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·João BotelhoLuísa Peixe
Feb 27, 2021·Evolution; International Journal of Organic Evolution·Kyle J CardRichard E Lenski
May 1, 2021·Genome Biology·Carolin M KobrasSamuel K Sheppard
May 9, 2021·Applied Microbiology and Biotechnology·Tomás G VillaAngeles Sánchez-Pérez
Jul 1, 2021·Clinical Microbiology Reviews·F BaqueroT M Coque

❮ Previous
Next ❯

Datasets Mentioned

BETA
NIPL00000000.1
PRJNA384009

Methods Mentioned

BETA
PCR
DNA Assay
Fusion Tribrid

Software Mentioned

PLINK
Proteome Discoverer
ImageJ
SPAdes
Xcalibur

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Related Papers

The Journal of Hospital Infection
R R MarplesB D Cookson
Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America
Kanokporn MongkolrattanothaiBarry M Gray
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences
Hui HuangQifeng Yi
© 2022 Meta ULC. All rights reserved