High Rate of Macrolide Resistance in<i>Staphylococcus aureus</i>Strains from Patients with Cystic Fibrosis Reveals High Proportions of Hypermutable Strains

Prunier, Anne-Laure; Malbruny, Brigitte; Laurans, M.; Brouard, J.; Duhamel, J.F.; Leclercq, Roland

doi:10.1086/374937

Cited by 184 publications

(170 citation statements)

References 35 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

Section: Cystic Fibrosis (Cf)mentioning

confidence: 83%

“…A high rate of macrolide resistance (i.e. the presence of mutations in the target site of erythromycin) in Staphylococcus aureus strains from patients with CF also revealed a high proportion of hypermutable strains (Prunier et al, 2003). Nevertheless, a high prevalence of hypermutable strains has been described, essentially in chronically infected patients (such as CF patients).…”

Section: Using Insertional Inactivation Of the Muts Gene Inmentioning

confidence: 99%

“…Of a small collection of 49 Staphylococcus aureus isolates from CF patients, only one showed a weak elevation in mutation frequency (three-to fourfold increase) compared with the laboratory reference strain . There was a higher proportion of hypermutator strains in 89 staphylococcal CF isolates (14.6 %) compared with a group of 74 non-CF controls (1.3 %) (Prunier et al, 2003).P. aeruginosa is the most relevant pathogen in terms of development of chronic lung infections in patients with chronic underlying diseases such as CF, bronchiectasis and chronic obstructive pulmonary disease.…”

mentioning

confidence: 96%

See 2 more Smart Citations

Bacterial hypermutation: clinical implications

Jolivet‐Gougeon

Kovács

Gall‐David

et al. 2011

Journal of Medical Microbiology

View full text Add to dashboard Cite

Heritable hypermutation in bacteria is mainly due to alterations in the methyl-directed mismatch repair (MMR) system. MMR-deficient strains have been described from several bacterial species, and all of the strains exhibit increased mutation frequency and recombination, which are important mechanisms for acquired drug resistance in bacteria. Antibiotics select for drug-resistant strains and refine resistance determinants on plasmids, thus stimulating DNA recombination via the MMR system. Antibiotics can also act as indirect promoters of antibiotic resistance by inducing the SOS system and certain error-prone DNA polymerases. These alterations have clinical consequences in that efficacious treatment of bacterial infections requires high doses of antibiotics and/or a combination of different classes of antimicrobial agents. There are currently few new drugs with low endogenous resistance potential, and the development of such drugs merits further research. IntroductionEradication of infectious diseases is constantly challenged by micro-organisms that develop new survival strategies. Previous studies suggest that mutational events play a predominant role in bacterial adaptation and confer a selective advantage (Chou et al., 2009;Cooper, 2007). Early experiments aimed at detecting mutators used mutagenized laboratory strains of bacteria, sometimes coupled with different selection strategies. LeClerc et al. (1996) reported high mutation frequency among Escherichia coli and Salmonella pathogens, challenging the theory that mutators were rare among bacterial populations. Taken together, these findings demonstrated that natural populations could respond to environmental selection in two ways, i.e. by enhanced mutation frequencies and by recombination. Transient mutator status, which involves reversion or recombination within the mutator alleles or depletion of the methyl-directed mismatch repair (MMR) system proteins, allows the organism to temporarily benefit from the elevated mutation frequency for adaptation while reducing the risk of accumulating deleterious mutations. Using a mathematical model, Rosche & Foster (1999) showed that transient hypermutators play a role in adaptive mutation in E. coli. Molecular mechanisms of hypermutationProteins involved in the DNA mismatch repair pathway help replace nucleotides introduced erroneously into the replicated DNA and also hinder recombination between non-identical DNA sequences. Deficiencies in any of the DNA mismatch repair pathway mechanisms can lead to a hypermutator phenotype. DNA repairSiegel & Bryson (1967) discovered the mutS gene in an azaserine-resistant derivative of E. coli that had a mutator phenotype and carried a deletion in the mutS gene. The majority of naturally occurring strong mutators have defects in the MMR system; the mutations are mainly in mutS (Oliver et al., 2002), but deletions in genes encoding beta-clamp proteins and in mutH, mutL and mutU (uvrD) have also been described (Fig. 1). Inactivation of basal excision repair genes, e.g. mutY, mutM, ...

show abstract

Section: Cystic Fibrosis (Cf)mentioning

confidence: 83%

Section: Using Insertional Inactivation Of the Muts Gene Inmentioning

confidence: 99%

mentioning

confidence: 96%

See 1 more Smart Citation

Bacterial hypermutation: clinical implications

Jolivet‐Gougeon

Kovács

Gall‐David

et al. 2011

Journal of Medical Microbiology

View full text Add to dashboard Cite

show abstract

“…S. aureus persists in the airways of people with CF for years and can develop a hypermutator phenotype that promotes adaptive changes, including SCVs, thought to facilitate survival of this organism within the CF airway. 84,85 SCVs are detected visually on laboratory agar plates and exhibit slower growth rates due to metabolic defects (eg, thymidine biosynthesis deficiency 86 ), and they therefore require special susceptibility testing. However, the testing method has not been standardized by the Clinical and Laboratory Standards Institute.…”

Section: Ic4 Small Colony Variant (Scv) S Aureusmentioning

confidence: 99%

Infection Prevention and Control Guideline for Cystic Fibrosis: 2013 Update

Saiman

Siegel

LiPuma

et al. 2014

Infect. Control Hosp. Epidemiol.

352

382

View full text Add to dashboard Cite

The 2013 Infection Prevention and Control (IP&C) Guideline for Cystic Fibrosis (CF) was commissioned by the CF Foundation as an update of the 2003 Infection Control Guideline for CF. During the past decade, new knowledge and new challenges provided the following rationale to develop updated IP&C strategies for this unique population:1. The need to integrate relevant recommendations from evidence-based guidelines published since 2003 into IP&C practices for CF. These included guidelines from the Centers for Disease Control and Prevention (CDC)/Healthcare Infection Control Practices Advisory Committee (HICPAC), the World Health Organization (WHO), and key professional societies, including the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). During the past decade, new evidence has led to a renewed emphasis on source containment of potential pathogens and the role played by the contaminated healthcare environment in the transmission of infectious agents. Furthermore, an increased understanding of the importance of the application of implementation science, monitoring adherence, and feedback principles has been shown to increase the effectiveness of IP&C guideline recommendations.2. Experience with emerging pathogens in the non-CF population has expanded our understanding of droplet transmission of respiratory pathogens and can inform IP&C strategies for CF. These pathogens include severe acute respiratory syndrome coronavirus and the 2009 influenza A H1N1. Lessons learned about preventing transmission of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant gram-negative pathogens in non-CF patient populations also can inform IP&C strategies for CF.

show abstract

“…S. aureus exploits the same mechanism for macrolide resistance [60]. The general mechanism of Fluoroquinolone resistance in S. aureus functions either by bringing a change in the chromosome responsible for the expression of topoisomerase IV or DNA gyrase or by inducing a multidrug resistance efflux pump.…”

Section: Dna Damage or Mutationmentioning

confidence: 99%

Surmounting antimicrobial resistance in the Millennium Superbug: Staphylococcus aureus

Saxena

Gomber

2010

Open Medicine

View full text Add to dashboard Cite

AbstractStaphylococcus aureus is the third most dreaded pathogen posing a severe threat due to its refractory behavior against the current armamentarium of antimicrobial drugs. This is attributed to the evolution of an array of resistance mechanisms responsible for morbidity and mortality globally. Local and international travel has resulted in the movement of drug resistant S. aureus clones from hospitals into communities and further into different geographical areas where they have been responsible for epidemic outbreaks. Thus, there is a dire necessity to refrain further cross movement of these multidrug resistant clones across the globe. The plausible alternative to prevent this situation is by thorough implementation of regulatory aspects of sanitation, formulary usage and development of new therapeutic interventions. Various strategies like exploring novel antibacterial targets, high throughput screening of microbes, combinatorial and synthetic chemistry, combinatorial biosynthesis and vaccine development are being extensively sought to overcome multidrug resistant chronic Staphylococcal infections. The majority of the antibacterial drugs are of microbial origin and are prone to being resisted. Anti-staphylococcal plant natural products that may provide a new alternative to overcome the refractory S.aureus under clinical settings have grossly been unnoticed. The present communication highlights the new chemical entities and therapeutic modalities that are entering the pharmaceutical market or are in the late stages of clinical evaluation to overcome multidrug resistant Staphylococcal infections. The review also explores the possibility of immunity and enzyme-based interventions as new therapeutic modalities and highlights the regulatory concerns on the prescription, usage and formulary development in the developed and developing world to keep the new chemical entities and therapeutic modalities viable to overcome antimicrobial resistance in S. aureus.

show abstract

High Rate of Macrolide Resistance inStaphylococcus aureusStrains from Patients with Cystic Fibrosis Reveals High Proportions of Hypermutable Strains

Cited by 184 publications

References 35 publications

Bacterial hypermutation: clinical implications

Bacterial hypermutation: clinical implications

Infection Prevention and Control Guideline for Cystic Fibrosis: 2013 Update

Surmounting antimicrobial resistance in the Millennium Superbug: Staphylococcus aureus

Contact Info

Product

Resources

About