Species-Wide Phylogenomics of the Staphylococcus aureus
            <i>Agr</i>
            Operon Revealed Convergent Evolution of Frameshift Mutations

Raghuram, Vishnu; Alexander, Ashley M.; Loo, Hui Qi; Petit, Robert A.; Goldberg, Joanna B.; Read, Timothy D.

doi:10.1128/spectrum.01334-21

Cited by 20 publications

(35 citation statements)

References 86 publications

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“…Sequences were grouped into clonal complexes using the eBURST algorithm [31]. The agr type was assigned using AgrVATE (v1.0.2) [32] and spa type using spaTyper (v0.3.1) [33]. Average nucleotide identities (ANI) were calculated using fastANI [34].…”

Section: Methodsmentioning

confidence: 99%

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosis Staphylococcus aureus isolates

Mossop

Robinson

Jiang

et al. 2023

Journal of Medical Microbiology

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Introduction. One third of people with CF in the UK are co-infected by both Staphylococcus aureus and Pseudomonas aeruginosa . Chronic bacterial infection in CF contributes to the gradual destruction of lung tissue, and eventually respiratory failure in this group. Gap Statement. The contribution of S. aureus to cystic fibrosis (CF) lung decline in the presence or absence of P. aeruginosa is unclear. Defining the molecular and phenotypic characteristics of a range of S. aureus clinical isolates will help further understand its pathogenic capabilities. Aim. Our objective was to use molecular and phenotypic tools to characterise twenty-five clinical S. aureus isolates collected from mono- and coinfection with P. aeruginosa from people with CF at the Royal Victoria Infirmary, Newcastle upon Tyne. Methodology. Genomic DNA was extracted and sequenced. Multilocus sequence typing was used to construct phylogeny from the seven housekeeping genes. A pangenome was calculated using Roary, and cluster of Orthologous groups were assigned using eggNOG-mapper which were used to determine differences within core, accessory, and unique genomes. Characterisation of sequence type, clonal complex, agr and spa types was carried out using PubMLST, eBURST, AgrVATE and spaTyper, respectively. Antibiotic resistance was determined using Kirby-Bauer disc diffusion tests. Phenotypic testing of haemolysis was carried out using ovine red blood cell agar plates and mucoid phenotypes visualised using Congo red agar. Results. Clinical strains clustered closely based on agr type, sequence type and clonal complex. COG analysis revealed statistically significant enrichment of COG families between core, accessory and unique pangenome groups. The unique genome was significantly enriched for replication, recombination and repair, and defence mechanisms. The presence of known virulence genes and toxins were high within this group, and unique genes were identified in 11 strains. Strains which were isolated from the same patient all surpassed average nucleotide identity thresholds, however, differed in phenotypic traits. Antimicrobial resistance to macrolides was significantly higher in the coinfection group. Conclusion. There is huge variation in genetic and phenotypic capabilities of S. aureus strains. Further studies on how these may differ in relation to other species in the CF lung may give insight into inter-species interactions.

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Section: Methodsmentioning

confidence: 99%

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosis Staphylococcus aureus isolates

Mossop

Robinson

Jiang

et al. 2023

Journal of Medical Microbiology

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“…Sequences were grouped into clonal complexes using the eBURST algorithm (30). The agr type was assigned using AgrVATE (v1.0.2) (31) and spa type using spaTyper (v0.3.1) (32). Average nucleotide identities (ANI) were calculated using fastANI (33).…”

Section: Methodsmentioning

confidence: 99%

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosisStaphylococcus aureusisolates

Mossop

Robinson

Jiang

et al. 2022

Preprint

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Introduction: One third of people with CF in the UK are co-infected by both Staphylococcus aureus and Pseudomonas aeruginosa. Chronic bacterial infection in CF contributes to the gradual destruction of lung tissue, and eventually respiratory failure in this group. Gap Statement: The contribution of S. aureus to cystic fibrosis (CF) lung decline in the presence or absence of P. aeruginosa is unclear. Defining the molecular and phenotypic characteristics of a range of S. aureus clinical isolates will help further understand its pathogenic capabilities. Aim: Our objective was to use molecular and phenotypic tools to characterise twenty-five clinical S. aureus isolates collected from mono- and coinfection with P. aeruginosa from people with CF at the Royal Victoria Infirmary, Newcastle upon Tyne. Methodology: Genomic DNA was extracted and sequenced. Multilocus sequence typing was used to construct phylogeny from the seven housekeeping genes. A pangenome was calculated using Roary. and cluster of Orthologous groups were assigned using eggNOG-mapper which were used to determine differences within core, accessory, and unique genomes. Characterisation of sequence type, clonal complex, agr and spa types was carried out using PubMLST, eBURST, AgrVATE and spaTyper, respectively. Antibiotic resistance was determined using Kirby Bauer disk diffusion tests. Phenotypic testing of haemolysis was carried out using ovine red blood cell agar plates and mucoid phenotypes visualised using Congo red agar. Results: Clinical strains clustered closely based on agr type, sequence type and clonal complex. COG analysis revealed statistically significant enrichment of COG families between core, accessory and unique pangenome groups. The unique genome was significantly enriched for replication, recombination and repair, and defence mechanisms. The presence of known virulence genes and toxins were high within this group, and unique genes were identified in 11 strains. Strains which were isolated from the same patient all surpassed average nucleotide identity thresholds, however, differed in phenotypic traits. Antimicrobial resistance to macrolides was significantly higher in the coinfection group. Conclusion: There is huge variation in genetic and phenotypic capabilities of S. aureus strains. Further studies on how these may differ in relation to other species in the CF lung may give insight into inter-species interactions.

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“…2c), is an agonist of both AgrC4 and AgrC1 but an inhibitor of AgrC2 and AgrC3 [28,29]. Recently Raghuram et al [32] developed a software tool (AgrVATE; github.com/VishnuRaghuram94/AgrVATE) to interrogate S. aureus agr variability and evolution. Analysis of ~40 000 S. aureus genomes revealed that the distribution of the four agr groups is ~60 % group I, ~22 % group II, ~14 % group III and ~2.5 % group IV [32].…”

Section: The S Aureus Agr Systemmentioning

confidence: 99%

“…Recently Raghuram et al [32] developed a software tool (AgrVATE; github.com/VishnuRaghuram94/AgrVATE) to interrogate S. aureus agr variability and evolution. Analysis of ~40 000 S. aureus genomes revealed that the distribution of the four agr groups is ~60 % group I, ~22 % group II, ~14 % group III and ~2.5 % group IV [32]. This extensive in silico analysis did not uncover any novel agr groups, intermediate AIPs or AIPs acquired from CONS.…”

Section: The S Aureus Agr Systemmentioning

confidence: 99%

“…DNA sequence analysis of agr-dysfunctional S. aureus clinical isolates has revealed frameshifts, insertions, deletions and substitutions in the agrBDCA operon [87,97,98,113,114]. In their analysis of over 40 000 S. aureus genomes Raghuram et al [32] found that >5 % had agr operon frameshifts. These were almost exclusively found in agrA and agrC with the latter having accumulated the greatest number of different mutations.…”

Section: Agr Dysfunction -The Molecular Basismentioning

confidence: 99%

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Quorum-sensing, intra- and inter-species competition in the staphylococci

et al. 2023

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In Gram-positive bacteria such as Staphylococcus aureus and the coagulase-negative staphylococci (CoNS), the accessory gene regulator (agr) is a highly conserved but polymorphic quorum-sensing system involved in colonization, virulence and biofilm development. Signalling via agr depends on the interaction of an autoinducing peptide (AIP) with AgrC, a transmembrane sensor kinase that, once phosphorylated activates the response regulator AgrA. This in turn autoinduces AIP biosynthesis and drives target gene expression directly via AgrA or via the post-transcriptional regulator, RNAIII. In this review we describe the molecular mechanisms underlying the agr-mediated generation of, and response to, AIPs and the molecular basis of AIP-dependent activation and inhibition of AgrC. How the environment impacts on agr functionality is considered and the consequences of agr dysfunction for infection explored. We also discuss the concept of AIP-driven competitive interference between S. aureus and the CoNS and its anti-infective potential.

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Species-Wide Phylogenomics of the Staphylococcus aureus Agr Operon Revealed Convergent Evolution of Frameshift Mutations

Abstract: Staphylococcus aureus is a globally pervasive pathogen that produces a plethora of toxic molecules that can harm host immune cells. Production of these toxins is mainly controlled by an active agr quorum-sensing system, which senses and responds to bacterial cell density.

Cited by 20 publications

References 86 publications

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosis Staphylococcus aureus isolates

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosis Staphylococcus aureus isolates

Characterisation of key genotypic and phenotypic traits of clinical cystic fibrosisStaphylococcus aureusisolates

Quorum-sensing, intra- and inter-species competition in the staphylococci

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