Prophage elements function as reservoir for antibiotic resistance and virulence genes in nosocomial pathogens

Abstract

Prophages are often involved in host survival strategies and contribute toward increasing the genetic diversity of the host genome. Prophages also drive horizontal propagation of various genes as vehicles. However, there are few retrospective studies contributing to the propagation of antimicrobial resistance (AMR) and virulence factor (VF) genes by prophage. In this study, we extracted complete genome sequences of seven pathogens, including ESKAPE bacteria and Escherichia coli deposited in a public database, and examined the distribution of both AMR and VF genes in certain genomic regions of prophage, including prophage-like element. We found that the ratios of AMR and VF genes greatly varied among the seven species. More than 55% of Enterobacter cloacae strains had VF genes, but only 0.8% of Klebsiella pneumoniae strains had VF genes from prophages. The prophage types carrying AMR genes were detected in a broad range of hosts, whereas prophages containing VF genes were conserved in only one or two species, suggesting that distribution patterns of prophages were different between prophages encoding AMR or VF genes. We also found that the prophage containing class 1 integrase possessed a significantly higher number of AMR genes than prophages with no class 1 integrase. Moreover, AMR genes in the prophage were located near transposase and integrase. The results of this study reveal a comprehensive picture of AMR and VF genes present in prophage elements and provide new insights into the horizontal transfer of genes associated with antimicrobial resistance and pathogenicity.ImportanceAlthough we believe phages play an important role in horizontal gene transfer in exchanging genetic material, we do not know the distribution of the antimicrobial resistance and/or virulence genes in prophages. We collected different prophage elements from the complete genome sequence of seven species – Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae, as well as Escherichia coli –, and characterized the distribution of antimicrobial resistance and virulence genes encoded in the prophage region. While virulence genes in prophage were found to be species-specific, antimicrobial resistance genes in prophages were highly conserved in various species. Integron structure was detected within prophage regions in almost all of the genera. Maximum of 11 antimicrobial resistance genes were found in a single prophage region, suggesting that prophages act as a reservoir for antimicrobial resistance genes. Our results highlight new insights on prophages as horizontal gene carriers.

Prophages encoding human immune evasion cluster genes are enriched in Staphylococcus aureus isolated from chronic rhinosinusitis patients with nasal polyps

“…Although gene density and prophage size are inversely correlated, phage associated genes (including those necessary for viral replication) were less frequent in incomplete prophages. Loss of phage associated genes like portal (critical roles in head assembly, genome packaging, neck/tail attachment, genome ejection), terminase (catalyse site-specific endo-nucleolytic cleavage of DNA and its packaging into phage proheads), lysin (cleave host’s cell wall), proteases (encapsulation of viral DNA into capsid) leads to permanent domestication of a prophage and yet still confers a selective advantage [65–68]. As most of the virulent phages of S.…”

“…Prophage encoded ARGs are sparsely reported in clinically important bacteria like Acinetobacter , Pseudomonas , Escherichia [16–18, 67, 71]. Also ARGs have been occasionally reported in S.…”

The Age of Phage: Friend or Foe in the New Dawn of Therapeutic and Biocontrol Applications?

“…Specifically, as active prophages may excise to form progeny phage particles which increase the mobility of carried virulence and resistance genes; the presence of cryptic prophages, considered as relatively permanent reservoirs of virulence, resistance, and tolerance genes due to their inability to form active phage particles to lyse their hosts, further laments the beneficial impact which prophages may have on bacterial survival [119]. Moreover, insight into the prevalence of virulence factors and antimicrobial resistance genes encoded by prophages in different strains of seven bacterial pathogens may suggest differing distribution patterns, with prophage-encoded antimicrobial resistance genes being detected in a broader range of hosts than prophages containing virulence factors, which were conserved in only a couple species [120]. However, more analysis is needed using more strains isolated from different clinical and natural environments before drawing a generalized conclusion from these observations.…”

Prophages in the infant gut are largely induced, and may be functionally relevant to their hosts

“…These genes are not essential for the phage itself, but may benefit the bacterial host by providing additional functionality [23]. These can include antibiotic resistance genes [24][25][26], and toxins or virulence genes that increase the fitness of pathogenic bacteria during infection [27][28][29]. The presence of a prophage within a bacteria also has the added benefit of being protective from infections.…”