Biology subjects

Rasigade, J.-P.

Publications and source records attributed to Rasigade, J.-P..

6 recordsLinked to original sources

bioRxiv2026

Heterogeneous dynamics of mobile genetic elements encode and spread antibiotic persistence in bacteria

Bacterial persisters are nonreplicating cells that transiently evade antibiotic killing within an otherwise susceptible, replicating population. While persister formation has traditionally been attributed to phenotypic heterogeneity, reversible functional variations among genetically identical cells, most studies lack direct genomic evidence to exclude the contribution of cryptic and reversible genetic variations. Here, we demonstrate that the dynamics of the Legionella pneumophila integrative and conjugative element (ICEs) pP36 encode and disseminate antibiotic persistence-like traits. During biofilm formation, pP36 undergoes heterogeneous chromosomal excision generating a subpopulation of nonreplicating persisters-like bacteria with a distinct molecular profile. pP36-mediated L. pneumophila growth rate heterogeneity significantly enhances bacterial survival under fluoroquinolone treatment. Our findings reveal that pP36 dynamics not only orchestrate physiological diversity but also serve as a vehicle for horizontal transfer of antibiotic persistence mechanisms among clinical Legionella isolates. While ICEs are recognized as key drivers of antibiotic resistance dissemination, this study establishes that ICEs-mediated phenotypic variations is a critical determinant of persister-like cell formation, reshaping our understanding of bacterial adaptability to antibiotic stress.

microbiology↗

bioRxiv2022

Staphylococcus aureus virulence factor expression matters: input from targeted proteomics shows Panton-Valentine leucocidin impact on mortality

In the case of commensal bacteria such as Staphylococcus aureus, the transition from commensalism to invasion and disease as well as disease severity in the course of an infection remain poorly predictable on the sole basis of virulence gene content. To determine whether variations in the levels of expression of the numerous S. aureus virulence factors could affect disease occurrence and/or severity, we developed a targeted proteomic approach that monitored 149 peptide surrogates targeting 44 proteins. Semi-quantification was achieved by normalization on the signal of ribosomal proteins. We then evaluated this approach on a series of S.aureus strains from 136 patients presenting a severe community-acquired pneumonia, all admitted to an intensive care unit. After adjusting to the Charlson Comorbidity Index score the multivariate analysis of severity parameters found that HlgB, Nuc, and Tsst-1 were positively associated while BlaI and HlgC were negatively associated with leucopenia. BlaZ and HlgB were positively associated with hemoptysis and HlgC was negatively associated with hemoptysis. Regarding mortality, both the multivariate (1.28; 95%CI[1.02;1.60]) and survival (1.15; 95%CI[1.016;1.302]) analyses showed that only PVL was associated with death in a dose-dependent manner. Beyond highlighting the decisive role of PVL in community-acquired pneumonia severity, this study brings the proof of concept that "expression matters" and proposes a method that can be routinely implemented in laboratories, for any Staphylococcal disease, and which could be developed for other commensal bacteria. One Sentence SummaryA highly multiplexed semi-quantitative mass spectrometry method was developed for 44 Staphylococcus aureus virulence factors; applied to a 136-strain collection from severe community-acquired pneumonia patients, it showed that Panton-Valentine leucocidin was the only factor to impact mortality in a dose-dependent manner.

microbiology↗

bioRxiv2022

All Staphylococcus aureus bacteraemia strains have the potential to cause infective endocarditis: results of GWAS and experimental animal studies

Abstract and KeywordsO_ST_ABSAimsC_ST_ABSInfective endocarditis (IE) complicates 10-20% of Staphylococcus aureus bacteraemia (SAB). We aimed to determine whether IE strains of S. aureus are genotypically different or behave differently in experimental endocarditis models as compared to non-IE SAB strains. Methods and ResultsWe conducted a genome wide association study (GWAS) of 924 S. aureus genomes from IE (274) and non-IE (650) SAB patients, and tested a subset of strains in two experimental animal models of IE, one studying the early step of bacterial adhesion to inflamed mice valves, the second evaluating the local and systemic developmental process of IE on mechanically damaged rabbit valves. The genetic profile of S. aureus IE and non-IE SAB strains did not differ when considering single nucleotide polymorphisms, coding sequences and k-mers analyses in GWASs. In the inflammation-induced IE model in mice no difference was observed between IE and non-IE SAB strains both in adhesion to the cardiac valves and in the propensity to cause IE; in the mechanical IE-induced rabbit model, there was no difference between IE and non-IE SAB strains regarding vegetation size and CFU. ConclusionS. aureus isolates from SAB patients with and without IE were indistinguishable, by GWAS and by two in vivo models of IE. Thus, S. aureus strain variation is not the primary determinant of IE. Pending the possible identification of host factors predisposing to IE, all strains of S. aureus must be considered in patients as capable of causing this common, lethal infection once they have accessed the bloodstream. Translational PerspectiveStaphylococcus aureus endocarditis (IE) is a deadly complication of S. aureus bacteraemia (SAB). Beyond well-identified host related IE risk factors, whether bacterial features may influence the occurrence of IE in the course of bacteraemia remain elusive. We analysed the genomes of 924 S. aureus strains from IE and non-IE SAB and compared some in two in vivo IE models. We demonstrated that the propensity of S. aureus to cause IE in the course of bacteraemia does not depend on the intrinsic genetic or virulence factors of S. aureus. These findings are of importance for the management of S. aureus bacteraemia.

microbiology↗

bioRxiv2020

Potential role of Mercury pollutants in the success of Methicillin-Resistant Staphylococcus aureus USA300 in Latin America

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) lineage known as USA300-North American (NA) has become highly prevalent in North America whilst a USA300 variant known as USA300-LV, harboring a mercury resistance element (COMER), has become dominant in South America. We investigated whether mercury pollution, which is common in South America notably because of artisanal gold mining, may explain the local dominance pattern of USA300-LV. Density-based estimation of epidemic success in 250 genomes of the ST8 lineage revealed that the acquisition of COMER in USA300 progenitors increased success in South American countries but decreased success elsewhere. The fitness of USA300-LV was impaired in vitro compared with USA300-NA, but the addition of sub-inhibitory concentration of mercury provided a strong fitness advantage to USA300-LV and triggered an overexpression of major virulence factors. The success of USA300-LV in South America may result from low-level mercury exposure selecting resistant and virulent strains.

microbiology↗

bioRxiv2019

Metapopulation ecology links antibiotic resistance, consumption and patient transfers in a network of hospital wards

Antimicrobial resistance (AMR) is a global threat. A better understanding of how antibiotic use and between ward patient transfers (or connectivity) impact hospital AMR can help optimize antibiotic stewardship and infection control strategies. Here, we used metapopulation ecology to explain variations in infection incidences of 17 ESKAPE pathogen variants in a network of 357 hospital wards. Multivariate models identified the strongest influence of ward-level antibiotic use on more resistant variants, and of connectivity on nosocomial species and carbapenem-resistant variants. Pairwise associations between infection incidence and the consumption of specific antibiotics were significantly stronger when such associations represented a priori AMR selection, suggesting that AMR evolves within the network. Piperacillin-tazobactam consumption was the strongest predictor of the cumulative incidence of infections resistant to empirical sepsis therapy. Our data establish that both antibiotic use and connectivity measurably influence hospital AMR and provide a ranking of key antibiotics by their impact on AMR.

ecology↗

bioRxiv2018

Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia

Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear.\n\nWe utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR-MTBC strains from Karakalpakstan, Uzbekistan (2001-2006).\n\nOne MTBC-clone (termed Central Asian outbreak, CAO) with resistance mediating mutations to eight anti-TB drugs existed prior the worldwide introduction of standardized WHO-endorsed directly observed treatment, short-course (DOTS). DOTS implementation in Karakalpakstan in 1998 likely selected for these CAO-strains, comprising 75% of sampled MDR-TB strains in 2005/2006. CAO-strains were also identified in a previously published cohort from Samara, Russia (2008-2010). Similarly, transmission success and resistance development was linked to mutations compensating fitness deficits associated with rifampicin resistance.\n\nThe genetic make-up of these outbreak clades threatens the success of both empirical and standardized guideline driven MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan.

evolutionary biology↗