Biology subjects

van Duin, D.

Publications and source records attributed to van Duin, D..

3 recordsLinked to original sources

bioRxiv2025

Protein Malnutrition Facilitates Intestinal Colonization with Highly Resistant Klebsiella pneumoniae

Pediatric infections with Highly Resistant Enterobacterales (HRE), including Klebsiella pneumoniae resistant to 3rd-generation cephalosporins and/or carbapenems, disproportionately affect low- and middle-income countries where malnutrition is prevalent. The underlying mechanisms linking malnutrition to HRE colonization in children have not been established. In this study we developed a mouse model of pediatric malnutrition and intestinal colonization with clinical isolates of carbapenem-resistant K. pneumoniae (CR-Kp). Juvenile mice fed a protein-deficient diet (PD) were more susceptible to intestinal colonization after inoculation with human-derived strains of CR-Kp, demonstrating a 3-4 log higher colonization burden in comparison to mice fed a control diet (CD). Colonization in PD-fed mice persisted for up to 6 weeks and CR-Kp were transmitted between PD-fed but not CD-fed cage mates. Antibiotic treatment resulted in similar CR-Kp colonization burdens regardless of diet, suggesting that nutrition-dependent colonization resistance is reliant on an intact microbiota. Secondary bile acids, a product of resident intestinal microbiota, were reduced in PD-fed and antibiotic treated mice and demonstrated an inverse correlation with CR-Kp burden. Secondary bile acids directly inhibited CR-Kp growth in vitro, suggesting that a loss of these inhibitory metabolites may mediate malnutrition-induced susceptibility to HRE colonization.

microbiology↗

bioRxiv2021

Carbapenem-Resistant Acinetobacter baumannii in US hospitals: diversification of circulating lineages and antimicrobial resistance

Carbapenem-resistant Acinetobacter baumannii (CRAb) are a major cause of healthcare-associated infections. CRAb are typically multidrug-resistant and infection is difficult to treat. Despite the urgent threat that CRAb pose, few systematic studies of CRAb clinical and molecular epidemiology have been conducted. The Study Network of Acinetobacter as a Carbapenem-Resistant Pathogen (SNAP) is designed to investigate the clinical characteristics and contemporary population structure of CRAb circulating in US hospital systems using whole genome sequencing (WGS). Analysis of the initial 120 SNAP patients from four US centers revealed that CRAb remain a significant threat to hospitalized patients, affecting the most vulnerable patients and resulting in 24% all-cause 30-day mortality. The majority of currently circulating isolates belonged to ST2Pas, a part of Clonal Complex 2 (CC2), which is the dominant drug-resistant lineage in the United States and Europe. We identified three distinct sub-lineages within CC2, which differed in their antibiotic resistance phenotypes and geographic distribution. Most concerning, colistin resistance (38%) and cefiderocol (10%) resistance were common within CC2 sub-lineage C (CC2C), where the majority of isolates belonged to ST2Pas/ST281Ox. Additionally, we identified a newly emergent lineage, ST499Pas that was the most common non-CC2 lineage in our study and had a more favorable drug susceptibility profile compared to CC2. Our findings suggest a shift within the CRAb population in the US during the past 10 years, and emphasize the importance of real-time surveillance and molecular epidemiology in studying CRAb dissemination and clinical impact. ImportanceCarbapenem-resistant Acinetobacter baumannii (CRAb) constitute a major threat to public health. To elucidate the molecular and clinical epidemiology of CRAb in the US, clinical CRAb isolates were collected along with data on patient characteristics and outcomes and bacterial isolates underwent whole genome sequencing and antibiotic susceptibility phenotyping. Key findings included emergence of new sub-lineages within the globally predominant clonal complex (CC) 2, increased colistin and cefiderocol resistance within one of the CC2 sub-lineages, and the emergence of ST499Pas as a previously unrecognized CRAb lineage in US hospitals.

microbiology↗

bioRxiv2020

Genomic Epidemiology of Escherichia coli Isolates from a Tertiary Referral Center in Lilongwe, Malawi

Antimicrobial resistance (AMR) is a global threat, including in sub-Saharan Africa. However, little is known about the genetics of resistant bacteria in the region. In Malawi, there is growing concern about increasing rates of antimicrobial resistance to most empirically used antimicrobials. The highly drug resistant Escherichia coli sequence type (ST) 131, which is associated with the extended spectrum {beta}-lactamase blaCTX-M-15, has been increasing in prevalence globally. Previous data from isolates collected between 2006-2013 in southern Malawi have shown the presence of ST131 and the blaCTX-M-15 gene in the country. We performed whole genome sequencing (WGS) of 58 clinical E. coli isolates at Kamuzu Central Hospital, a tertiary care center in central Malawi, collected from 2012-2018. We used Oxford Nanopore Technologies (ONT) sequencing, which was performed in Malawi. We show that ST131 has become more prevalent (14.9% increasing to 32.8%) and that the blaCTX-M-15gene is occurring at a higher frequency (21.3% increasing to 44.8%). Phylogenetics show isolates are highly related between the central and southern geographic regions and confirm that ST131 isolates are contained in a single group consistent with recent expansion. All AMR genes, including blaCTX-M-15, were widely distributed across sequence types. We also identified an increased number of ST410 isolates, which in this study tend to carry a plasmid-located copy of blaCTX-M-15 gene at a higher frequency than blaCTX-M-15 occurs in ST131. This study confirms the expanding nature of ST131 and the wide distribution of the blaCTX-M-15 gene in Malawi. We also highlight the feasibility of conducting longitudinal genomic epidemiology studies of important bacteria with the sequencing done on site using a nanopore platform that requires minimal infrastructure. DATA SUMMARYThe sequencing data used for this analysis is available in public data repositories. Information on the sequences used is provided in Supplementary Table 2.

genetics↗