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Prophages Present in Acinetobacter pittii Influence Bacterial Virulence, Antibiotic Resistance, and Genomic Rearrangements.

ABSTRACT: Introduction: Antibiotic resistance and virulence are common among bacterial populations, posing a global clinical challenge. The bacterial species Acinetobacter pittii, an infectious agent in clinical environments, has shown increasing rates of antibiotic resistance. Viruses that integrate as prophages into A. pittii could be a potential cause of this pathogenicity, as they often contain antibiotic resistance or virulence factor gene sequences. Methods: In this study, we analyzed 25 A. pittii strains for potential prophages. Using virulence factor databases, we identified many common and virulent prophages in A. pittii. Results: The analysis also included a specific catalogue of the virulence factors and antibiotic resistance genes contributed by A. pittii prophages. Finally, our results illustrate multiple similarities between A. pittii and its bacterial relatives with regard to prophage integration sites and prevalence. Discussion: These findings provide a broader insight into prophage behavior that can be applied to future studies on similar species in the Acinetobacter calcoaceticus-baumannii complex.

SUBMITTER: Zhu R

PROVIDER: S-EPMC9041518 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Prophages Present in Acinetobacter pittii Influence Bacterial Virulence, Antibiotic Resistance, and Genomic Rearrangements.

Zhu Richard R Mathur Vinayak V

PHAGE (New Rochelle, N.Y.) 20220318 1

Introduction: Antibiotic resistance and virulence are common among bacterial populations, posing a global clinical challenge. The bacterial species Acinetobacter pittii, an infectious agent in clinical environments, has shown increasing rates of antibiotic resistance. Viruses that integrate as prophages into A. pittii could be a potential cause of this pathogenicity, as they often contain antibiotic resistance or virulence factor gene sequences. Methods: ...[more]

PMID: 36161193

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Project description:Acinetobacter pittii has increasingly been associated with several types of hospital-acquired severe infections. Genes implicated in carbapenem resistance, tigecycline resistance, or genes encoding extended spectrum cephalosporinases, such as blaADC, are commonly found in isolates implicated in these infections. A. pittii strains that are pandrug resistant have occasionally been identified. Food for human consumption, animals and plants are environmental sources of this pathogen. An alarming situation is that A. pitti has been identified as responsible for outbreaks in different regions worldwide. In this study, 384 genomes of A. pittii were analyzed, comprising sequences from clinical and non-clinical origins from 32 countries. The objective was to investigate if clinical strains possess genetic traits facilitating hospital adaptation. Results indicate significant genomic variability in terms of size and gene content among A. pittii isolates. The core genome represents a small portion (25-36%) of each isolate's genome, while genes associated with antibiotic resistance and virulence predominantly belong to the accessory genome. Notably, antibiotic resistance genes are encoded by a diverse array of plasmids. As the core genome between environmental and hospital isolates is the same, we can assume that hospital isolates acquired ARGs due to a high selective pressure in these settings. The strain's phylogeographic distribution indicates that there is no geographical bias in the isolate distribution; isolates from different geographic regions are dispersed throughout a core genome phylogenetic tree. A single clade may include isolates from extremely distant geographical areas. Furthermore, strains isolated from the environment or animal, or plant sources frequently share the same clade as hospital isolates. Our analysis showed that the clinical isolates do not already possess specific genes, other than antibiotic-resistant genes, to thrive in the hospital setting.

Project description:Acinetobacter baumannii is an opportunistic pathogen of increasing importance due to its propensity for intractable multidrug-resistant infections in hospitals. All clinical isolates examined contain a conserved gene cluster, the K locus, which determines the production of complex polysaccharides, including an exopolysaccharide capsule known to protect against killing by host serum and to increase virulence in animal models of infection. Whether the polysaccharides determined by the K locus contribute to intrinsic defenses against antibiotics is unknown. We demonstrate here that mutants deficient in the exopolysaccharide capsule have lowered intrinsic resistance to peptide antibiotics, while a mutation affecting sugar precursors involved in both capsule and lipopolysaccharide synthesis sensitizes the bacterium to multiple antibiotic classes. We observed that, when grown in the presence of certain antibiotics below their MIC, including the translation inhibitors chloramphenicol and erythromycin, A. baumannii increases production of the K locus exopolysaccharide. Hyperproduction of capsular exopolysaccharide is reversible and non-mutational, and occurs concomitantly with increased resistance to the inducing antibiotic that is independent of the presence of the K locus. Strikingly, antibiotic-enhanced capsular exopolysaccharide production confers increased resistance to killing by host complement and increases virulence in a mouse model of systemic infection. Finally, we show that augmented capsule production upon antibiotic exposure is facilitated by transcriptional increases in K locus gene expression that are dependent on a two-component regulatory system, bfmRS. These studies reveal that the synthesis of capsule, a major pathogenicity determinant, is regulated in response to antibiotic stress. Our data are consistent with a model in which gene expression changes triggered by ineffectual antibiotic treatment cause A. baumannii to transition between states of low and high virulence potential, which may contribute to the opportunistic nature of the pathogen.

Dataset Information

Prophages Present in Acinetobacter pittii Influence Bacterial Virulence, Antibiotic Resistance, and Genomic Rearrangements.

Publications

Prophages Present in <i>Acinetobacter pittii</i> Influence Bacterial Virulence, Antibiotic Resistance, and Genomic Rearrangements.

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