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

Abstract

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.

The giant staphylococcal protein Embp facilitates colonization of surfaces through Velcro-like attachment to fibrillated fibronectin

“…This discovery has implications for our understanding of how S. epidermidis colonizes host tissue and biomedical implants. Colonization and biofilm formation is the only virulence factor of S. epidermidis pathogensis, and it is therefore imperative to cause invasive diseases ( 28 ). Implants are hot-spots for biofilm formation because they offer a surface for attachment.…”

The road to success of coagulase-negative staphylococci: clinical significance of small colony variants and their pathogenic role in persistent infections

“…The success of S. epidermidis as a pathogen depends on its ability to flexibly adapt to environmental stresses, such as antimicrobial treatment, limited oxygen, or temperature fluctuations [77]. Bacteria can quickly respond to unfavorable environmental or stressful conditions by undergoing dynamic evolutionary changes and switch to SCV mode of growth which can provide a strong advantage and promote their survival [78].…”

“…Persisting bacterial pathogens have therefore developed different strategies to successfully evade the host innate response and establish an intracellular infection. To survive inside the hostile intracellular environment, SCVs manipulate the host cellular signaling pathways to avoid activation of the host immune response or cytotoxic effects in order to create an immune tolerant environment [11,77]. Activated macrophages provide an inhospitable environment for most microorganisms, and the phagolysosome is the definitive antimicrobial organelle [103].…”

Extensive Horizontal Gene Transfer within and between Species of Coagulase-Negative Staphylococcus

“…While almost all CoNS species generate infections given opportune environmental conditions ( Becker et al 2014 ), a few CoNS species are particularly notable. Staphylococcus epidermidis and Staphylococcus haemolyticus are most commonly associated with infections of indwelling or implanted foreign bodies ( Ahmed et al 2019 ; Both et al 2021 ). Staphylococcus saprophyticus is the common cause of urinary tract infections ( Widerström et al 2007 ; Lawal et al 2021 ), whereas Staphylococcus lugdunensis can cause infectious endocarditis ( Non and Santos 2017 ).…”