Search bioRxiv⌕ Search

bioRxiv · 10.1101/2023.09.03.556112

Examining the role of Acinetobacter baumannii Plasmid Types in Disseminating Antimicrobial Resistance

Abstract

Acinetobacter baumannii is a Gram-negative pathogen responsible for hospital-acquired infections with high levels of antimicrobial resistance (AMR). The spread of multidrug-resistant A. baumannii strains, particularly those resistant to carbapenems, has become a global concern. Spread of AMR in A. baumannii is primarily mediated by the acquisition of AMR genes through mobile genetic elements, such as plasmids. Thus, a comprehensive understanding of the role of different plasmid types in disseminating AMR genes is essential. In this study, we analysed the distribution of plasmid types, sampling sources, geographic locations, and AMR genes carried on A. baumannii plasmids. A collection of 814 complete plasmid entries was collated and analysed. Most plasmids were identified in clinical isolates from East Asia, North America, South Asia, West Europe, and Australia. We previously devised an Acinetobacter Plasmid Typing (APT) scheme where rep/Rep types were defined using 95% nucleotide identity and updated the scheme in this study by adding 13 novel rep/Rep types (93 types total). The APT scheme now includes 178 Rep variants belonging to three families: R1, R3, and RP. R1-type plasmids were mainly associated with global clone 1 strains, while R3-type plasmids were highly diverse and carried a variety of AMR determinants including carbapenem, aminoglycoside and colistin resistance genes. Similarly, RP-type and rep-less plasmids were also identified as important carriers of aminoglycoside and carbapenem resistance genes. This study provides a comprehensive overview of the distribution and characteristics of A. baumannii plasmids, shedding light on their role in the dissemination of AMR genes. The updated APT scheme and novel findings enhance our understanding of the molecular epidemiology of A. baumannii and provide valuable insights for surveillance and control strategies. IMPORTANCEA. baumannii has emerged as a major cause of nosocomial infections, particularly in intensive care units, posing a substantial challenge to patient safety and healthcare systems. Plasmids, which carry antimicrobial resistance (AMR) genes, play a crucial role in the multidrug resistance exhibited by A. baumannii strains, necessitating a comprehensive understanding of plasmid spread, and how to track them. This study provides important insights into A. baumannii plasmid epidemiology, and the extent of their role in spreading clinically significant AMR genes and how they are differentially distributed across different clones i.e. sequence types (STs) and geographical regions. These insights are important for identifying high-risk areas or clones implicated in plasmid transmission, in the context of the spread of multidrug-resistant A. baumannii strains. It also highlights the involvement of R3-type, RP-type and rep-less plasmids in the acquisition and spread of significant AMR genes including those conferring resistance to carbapenems, aminoglycosides and colistin.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lam, M. M. C., Hamidian, M.. 2023-09-03. Examining the role of Acinetobacter baumannii Plasmid Types in Disseminating Antimicrobial Resistance. https://doi.org/10.1101/2023.09.03.556112

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

A conserved cysteine-histidine-glutamate metal site identifies DUF501 (Rv1025), an essential uncharacterised protein family of Mycobacterium tuberculosis, as a candidate metalloenzyme and drug target

A substantial fraction of the Mycobacterium tuberculosis proteome remains functionally uncharacterised. Rv1025, a 155-residue protein carrying the domain of unknown function DUF501 (Pfam PF04417), is essential by transposon mutagenesis and vulnerable by CRISPR interference, an attractive but neglected drug target, yet has never been functionally described. The family (4,370 proteins, no Gene Ontology term, no solved structure) is uncharacterised across all organisms and essential in three Actinobacterial genera. A Foldseek search of the AlphaFold model against complete structural databases finds no significant homolog, indicating a novel fold. The operon eno-divIC-Rv1025-ppx2 is conserved across the Actinobacteria phylum, yet AlphaFold-Multimer finds no direct complex between Rv1025 and its neighbour DivIC. Instead, conservation across 8,700 homologous sequences reveals a near-invariant Cys113-His115-Glu59 cluster forming a pocket. Holo AlphaFold3 predictions with Zn, Fe and Mn confidently place a divalent metal on this triad at 2.25-2.47 A; mutating the triad relocates the metal, and an independent backbone-geometry predictor recovers the same site, confirming specificity. The triad is universal across the family: present in all 1,472 near-complete bacterial sequences of the Pfam alignment, with no non-conservative substitution among the 2,228 sequences examined, a defining feature of bacterial DUF501 rather than a mycobacterial peculiarity. We propose that DUF501 is a metal-binding protein and candidate metalloenzyme, the first functional hypothesis for this family, whose conserved, essential metal pocket is a promising drug target. As the predictions build on a conservation-defined site within a fully computational study, they are supportive rather than proof of metal occupancy and warrant experimental validation.

microbiology↗

Mycoplasmal endosymbionts of Trichomonas vaginalis are associated with reduced risk for Chlamydia trachomatis endometrial infection in asymptomatic, coinfected, women.

Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis, the most common curable non-viral sexually transmitted infection, and Chlamydia trachomatis is a bacterial pathogen that can ascend to the upper genital tract and cause pelvic inflammatory disease, infertility, and ectopic pregnancy. T. vaginalis harbors bacterial endosymbionts, including Candidatus Malacoplasma girerdii, an obligate symbiont, and Metamycoplasma hominis, which can live freely or symbiotically. In a 16S rRNA sequencing study of the cervicovaginal microbiome of women at high risk for chlamydial infection, Ca. M. girerdii abundance was one of 13 features predicting lack of chlamydial spread to the endometrium, despite no direct association between T. vaginalis infection and reduced chlamydial ascension. Investigating the relationship between these microorganisms further, we found that T. vaginalis vaginal abundance correlated positively with chlamydial burden in women whose infection was confined to the cervix, while a nonsignificant inverse relationship was seen in women with endometrial spread. Among participants with high chlamydial burden, Ca. M. girerdii was detected exclusively in women without endometrial infection. Both endosymbionts trended toward more frequent detection, and higher abundance, in coinfected women without endometrial spread, while M. hominis abundance correlated strongly with T. vaginalis burden in this group. These findings suggest that mycoplasmal endosymbionts of T. vaginalis, rather than T. vaginalis itself, are microbial factors limiting chlamydial ascension, and point to a three-way interaction between parasite, endosymbiont, and bacterial pathogen that shapes upper genital tract C. trachomatis infection risk.

microbiology↗

Understanding the physiological alterations of Vibrio cholerae upon exposure to L-ascorbic acid

The scourge of cholera remains a major global public health threat. It affects up to 4 million people worldwide and causes tens of thousands of deaths each year. The disease is experiencing a concerning resurgence in many parts of Africa, the Middle East, and Asia. To effectively tackle cholera and circumvent rising antimicrobial resistance, targeted biological and preventive approaches, complementing traditional rehydration, are urgently needed. In this regard, our group has demonstrated the efficacy of L-ascorbic acid in controlling the growth and pathogenesis of Vibrio cholerae in vitro. The present work further provides a mechanistic elucidation of the L-ascorbic acid-mediated physiological changes in V. cholerae and also bolsters such a non-antibiotic approach to control cholera.

microbiology↗