Biology subjects

Davong, V.

Publications and source records attributed to Davong, V..

3 recordsLinked to original sources

bioRxiv2022

The highly diverse and complex plasmid population found in Escherichia coli colonising travellers to Laos and their role in antimicrobial resistance gene carriage

Increased colonisation by antimicrobial resistant organisms is closely associated with international travel. This study investigated the diversity of mobile genetic elements involved with antimicrobial resistance (AMR) gene carriage in extended-spectrum beta-lactamase (ESBL) -producing Escherichia coli that colonised travellers to Laos. Long-read sequencing was used to reconstruct complete plasmid sequences from 49 isolates obtained from the daily stool samples of 23 travellers over a three-week period. This method revealed a collection of 105 distinct plasmids, 38.1% of which carried AMR genes. The plasmids in this population were diverse, mostly unreported and included 38 replicon types, with F-type plasmids (n=22) the most prevalent amongst those carrying AMR genes. Fine-scale analysis of all plasmids identified numerous AMR gene contexts and emphasised the importance of IS elements, specifically members of the IS6/IS26 family, in the creation of complex multi-drug resistance regions. We found a concerning convergence of ESBL and colistin resistance determinants, with three plasmids from two different F-type lineages carrying blaCTX-M and mcr genes. The extensive diversity seen here highlights the worrying probability that stable new vehicles for AMR will evolve in E. coli populations that can disseminate internationally through travel networks. Impact StatementThe global spread of AMR is closely associated with international travel. AMR is a severe global concern and has compromised treatment options for many bacterial pathogens, among them pathogens carrying ESBL and colistin resistance genes. Colonising MDR organisms have the potential to cause serious consequences. Infections caused by MDR bacteria are associated with longer hospitalisation, poorer patient outcomes, greater mortality, and higher costs compared to infections with susceptible bacteria. This study elucidates the numerous different types of plasmids carrying AMR genes in colonising ESBL-producing E. coli isolates found in faecal samples from in travellers to Vientiane, Laos. Here we add to known databases of AMR plasmids by adding these MDR plasmids found in Southeast Asia, an area of high AMR prevalence. We characterised novel AMR plasmids including complex ESBL (blaCTX-M) and colistin (mcr) resistance co-carriage plasmids, emphasising the potential exposure of travellers to Laos to a wide variety of mobile genetic elements that may facilitate global AMR spread. This in-depth study has revealed further detail of the numerous factors that may influence AMR transfer, therefore potential routes of AMR spread internationally, and is a step towards finding methods to combat AMR spread. Data SummaryLong-read sequencing data is available through National Center for Biotechnology Information under the BioProject PRJNA853172. Complete plasmid sequences have been uploaded to GenBank with accession numbers in supplementary S1. The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

microbiology↗

bioRxiv2019

Real-time sampling of travelers shows intestinal colonization by multidrug-resistant bacteria to be a dynamic process with multiple transient acquisitions

BackgroundAntimicrobial resistance (AMR) is highly prevalent in low- and middle-income countries (LMIC). International travel contributes substantially to the global spread of intestinal multidrug-resistant gram-negative (MDR-GN) bacteria. Of the 100 million annual visitors to LMIC, 30-70% become colonized by MDR-GN bacteria. The phenomenon has been well documented, but since sampling has only been conducted after travelers return home, data on the actual colonization process are scarce. We aimed to characterize colonization dynamics by exploring stool samples abroad on a daily basis while visiting LMIC. MethodsA group of 20 European volunteers visiting Lao Peoples Democratic Republic for three weeks provided daily stool samples and filled in daily questionnaires. Acquisition of extended-spectrum beta-lactamase-producing gram-negative bacteria (ESBL-GN) was examined by selective stool cultures followed by whole-genome sequencing (WGS) of isolates. ResultsWhile colonization rates were 70% at the end of the study, daily sampling revealed that all participants had acquired ESBL-GN at some time point during their overseas stay, the colonization status varying day by day. WGS analysis ascribed the transient pattern of colonization to sequential acquisition of new strains, resulting in a loss of detectable colonization by the initial MDR-GN strains. All but one participant acquired multiple strains (n=2-7). Of the total of 83 unique strains identified (53 E. coli, 10 Klebsiella, 20 other ESBL-GN species), some were shared by as many as four subjects. ConclusionsThis is the first study to characterize in real time the dynamics of acquiring MDR-GN during travel. Our data show multiple transient colonization events indicative of constant microbial competition.

microbiology↗

bioRxiv2017

MULTILOCUS SEQUENCE TYPING REVEALS A UNIQUE CO-DOMINANT POPULATION STRUCTURE OF CRYPTOCOCCUS NEOFORMANS VAR. GRUBII IN VIETNAM

Cryptococcosis is amongst the most important invasive fungal infections globally, with cryptococcal meningitis causing an estimated 180,000 deaths each year in HIV infected patients alone. Patients with other forms of immunosuppression are also at risk, and disease is increasingly recognized in apparently immunocompetent individuals. Cryptococcus neoformans var. grubii (serotype A, molecular type VNI) has a global distribution and is responsible for the majority of cases. Here, we used the consensus ISHAM Multilocus Sequence Typing (MLST) for C. neoformans to define the population structure of clinical isolates of Cryptococcus neoformans var. grubii from Vietnam (n=136) and Laos (n=81). We placed these isolates into the global context using published MLST data from 8 other countries (total N = 669). We observed a phylo-geographical relationship in which Laos was similar to its Southeast Asian neighbor Thailand in being dominated (83%) by Sequence Type (ST) 4 and its Single Locus Variant ST6. On the other hand, Vietnam was uniquely intermediate between Southeast Asia and East Asia having both ST4/ST6 (35%) and ST5 (48%) which causes the majority of cases in East Asia. Analysis of genetic distance (Fst) between different populations of Cryptococcus neoformans var. grubii supported the intermediate nature of the population from Vietnam. A strong association between ST5 and infection in apparently immunocompetent, HIV-uninfected patients was observed in Vietnam (OR: 7.97, [95%CI: 3.18-19.97], p < 0.0001). Our study emphasizes that Vietnam, with its intermediate Cryptococcus neoformans var. grubii population structure, provides the strongest epidemiological evidence of the relationship between ST5 and infection of HIV-uninfected patients. Human population genetic distances within the region suggest these differences in CNVG population across Southeast Asia are driven by ecological factors rather than host factors.\n\nAuthor summaryCryptococcus neoformans is a yeast that causes meningitis in people, usually with damaged immune systems. There are >180,000 deaths in HIV-infected patients each year, most occurring where there are the highest HIV/AIDS disease burdens. Vietnam and Laos have contributed significantly to clinical trials aiming to improve the treatment of cryptococcal meningitis, but the relationship of isolates from these countries to the global population is not yet described. Here, we address this knowledge gap by using Multilocus Sequence Typing to study the population of Cryptococcus neoformans var. grubii (CNVG) in Laos and Vietnam, with the specific aim of incorporating these populations into the wider global context. We found that, in most countries, a single lineage (family) of strains was responsible for most disease. The Vietnamese CNVG population was unusual in that 2 main lineages circulated at the same time. The Vietnamese CNVG population occupies a middle ground between Thailand/Laos in the west and China in the east. The differences in population structure moving from West to East are probably due to ecological differences. Disease in HIV uninfected patients was almost always due to members of a single family of strains (ST5).

molecular biology↗