In-host evolution of Staphylococcus epidermidis in a pacemaker-associated endocarditis resulting in increased antibiotic tolerance

Haunreiter, Vanina Dengler; Boumasmoud, Mathilde; Häffner, Nicola; Wipfli, Dennis; Leimer, Nadja; Rachmühl, Carole; Kühnert, Denise; Achermann, Yvonne; Zbinden, Reinhard; Benussi1,, Stefano; Vulin, Clément; Zinkernagel, Annelies S.

doi:10.1038/s41467-019-09053-9

Cited by 73 publications

(57 citation statements)

References 59 publications

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“…Loss of Agr function has previously been described as a contributing factor in infections caused by Staphylococcus sp .. It appears to contribute towards a phenotype furthering immune evasion, such as increased biofilm formation and reduced production of PSMs [ 43 – 46 ]. We did not observe any non-synonymous SNPs (nsSNPs) or small insertions or deletions in agrBDCA .…”

Section: Resultsmentioning

confidence: 99%

Distinct clonal lineages and within-host diversification shape invasive Staphylococcus epidermidis populations

Both

Huang

et al. 2021

PLoS Pathog

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S. epidermidis is a substantial component of the human skin microbiota, but also one of the major causes of nosocomial infection in the context of implanted medical devices. We here aimed to advance the understanding of S. epidermidis genotypes and phenotypes conducive to infection establishment. Furthermore, we investigate the adaptation of individual clonal lines to the infection lifestyle based on the detailed analysis of individual S. epidermidis populations of 23 patients suffering from prosthetic joint infection. Analysis of invasive and colonizing S. epidermidis provided evidence that invasive S. epidermidis are characterized by infection-supporting phenotypes (e.g. increased biofilm formation, growth in nutrient poor media and antibiotic resistance), as well as specific genetic traits. The discriminating gene loci were almost exclusively assigned to the mobilome. Here, in addition to IS256 and SCCmec, chromosomally integrated phages was identified for the first time. These phenotypic and genotypic features were more likely present in isolates belonging to sequence type (ST) 2. By comparing seven patient-matched nasal and invasive S. epidermidis isolates belonging to identical genetic lineages, infection-associated phenotypic and genotypic changes were documented. Besides increased biofilm production, the invasive isolates were characterized by better growth in nutrient-poor media and reduced hemolysis. By examining several colonies grown in parallel from each infection, evidence for genetic within-host population heterogeneity was obtained. Importantly, subpopulations carrying IS insertions in agrC, mutations in the acetate kinase (AckA) and deletions in the SCCmec element emerged in several infections. In summary, these results shed light on the multifactorial processes of infection adaptation and demonstrate how S. epidermidis is able to flexibly repurpose and edit factors important for colonization to facilitate survival in hostile infection environments.

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Section: Resultsmentioning

confidence: 99%

Distinct clonal lineages and within-host diversification shape invasive Staphylococcus epidermidis populations

Both

Huang

et al. 2021

PLoS Pathog

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“…However, the high tolerance of CoNS biofilm cells commonly causes the failure of antibiotics, even when the most severe therapies are used [214] and, in the cases associated with the use of IMD, may implicate the removal of the infected device, resulting in prolonged hospital stays and increased morbidity and mortality rates [42,203,215]. Interestingly, the problematic of IMD-associated infections was emphasized by a recent study that assessed S. epidermidis in-host evolution in a case of pacemaker-associated endocarditis, which has shown that increased tolerance to antibiotics and capacity to form biofilms occurred during the course of infection [216]. This helps to explain the often inefficacy of antibiotics to treat S. epidermidis infections.…”

Section: Antibiotic Resistancementioning

confidence: 99%

Virulence Factors in Coagulase-Negative Staphylococci

et al. 2021

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Coagulase-negative staphylococci (CoNS) have emerged as major pathogens in healthcare-associated facilities, being S. epidermidis, S. haemolyticus and, more recently, S. lugdunensis, the most clinically relevant species. Despite being less virulent than the well-studied pathogen S. aureus, the number of CoNS strains sequenced is constantly increasing and, with that, the number of virulence factors identified in those strains. In this regard, biofilm formation is considered the most important. Besides virulence factors, the presence of several antibiotic-resistance genes identified in CoNS is worrisome and makes treatment very challenging. In this review, we analyzed the different aspects involved in CoNS virulence and their impact on health and food.

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“…This will further increase the time duration required for killing the bacterial population. Recent clinical studies have shown in-host evolution of antibiotic tolerance in other pathogenic bacteria and its association with treatment complications (21).…”

Section: Introductionmentioning

confidence: 99%

Most-Probable-Number-Based Minimum Duration of Killing Assay for Determining the Spectrum of Rifampicin Susceptibility in Clinical Mycobacterium tuberculosis Isolates

Vijay

Nhung

Bao

et al. 2021

Antimicrob Agents Chemother

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Accurate antibiotic susceptibility testing is essential for successful tuberculosis treatment. Recent studies have highlighted the limitations of minimum inhibitory concentrations (MIC) based phenotypic susceptibility methods in detecting other aspects of antibiotic susceptibilities in bacteria. Duration and peak of antibiotic exposure, at or above the MIC required for killing the bacterial population, has emerged as another important factor for determining the antibiotic susceptibility. This is broadly defined as antibiotic tolerance. Antibiotic tolerance can further facilitate the emergence of antibiotic resistance. Currently there are limited methods to quantify antibiotic tolerance among clinical M. tuberculosis isolates. In this study, we develop a most-probable number (MPN) based minimum duration of killing (MDK) assay to quantify the spectrum of M. tuberculosis rifampicin susceptibility within subpopulations, based on time duration of rifampicin exposure required for killing the bacterial population. MDK90-99 and MDK99.99 defined as the minimum time duration of antibiotic exposure at or above MIC required for killing 90-99% and 99.99% of the initial (pre-treatment) bacterial population respectively. Results from the rifampicin MDK assay applied to 28 laboratory and clinical M. tuberculosis isolates showed that there is variation in rifampicin susceptibility among isolates. Rifampicin MDK99/99.99 time for isolates varied from less than 2 to 10 days. MDK was correlated with larger sub-populations of M. tuberculosis from clinical isolates that were rifampicin tolerant. Our study demonstrates the utility of MDK assays to measure the variation in antibiotic tolerance among clinical M. tuberculosis isolates and further expands clinically important aspects of antibiotic susceptibility testing.

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In-host evolution of Staphylococcus epidermidis in a pacemaker-associated endocarditis resulting in increased antibiotic tolerance

Cited by 73 publications

References 59 publications

Distinct clonal lineages and within-host diversification shape invasive Staphylococcus epidermidis populations

Distinct clonal lineages and within-host diversification shape invasive Staphylococcus epidermidis populations

Virulence Factors in Coagulase-Negative Staphylococci

Most-Probable-Number-Based Minimum Duration of Killing Assay for Determining the Spectrum of Rifampicin Susceptibility in Clinical Mycobacterium tuberculosis Isolates

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