Virulence

-m virulence

The virulence module screens Staphylococcus aureus genomes for major toxin genes associated with specific clinical syndromes.

The Panton-Valentine Leukocidin (PVL), encoded by the subunits lukF-PVL and lukS-PVL, is an exotoxin responsible of skin and soft-tissue infection, and in some cases of life-threatening infections (ex- necrotizing pneumonia) (Shallcross et al. 2013; Hoppe et al. 2019; Labandeira-Rey et al. 2007). Other two important leukocidins, are lukD and lukE, which enhance virulence and contribute to Staphylococcus aureus pathogenesis (Alonzo et al. 2012).

The Toxic Shock Syndrome Toxin-1 (TSST-1) is an enterotoxin associated with the development of the toxic shock syndrome, a severe life-threatening condition (Manosur et al. 2021)

The exofoliative toxin etA, etB, etD, and etE can cause the staphylococcal scaled skin syndrome (SSSS), a severe infection (Nishifuji et al. 2008).

The Staphylococcal enterotoxins (SE) are mainly responsible of food poisoning, and are classified as superantigens, due to the ability to stimulate large populations of T cells (Pinchuk et al. 2010; Choi et al. 1989).

A curated FASTA file containing representative virulence gene sequences is bundled with the module and stored in the /data directory.

All detected genes are annotated as follows:

  • No annotation: exact nucleotide match
  • ^: inexact nucleotide match but perfect amino acid match
  • *: inexact nucleotide and inexact amino acid match
  • ?: incomplete match
  • -X%: truncated amino acid sequence

Parameters

Hits are filtered using minimum alignment identity and coverage thresholds:

  • --min_id_vir
    Minimum alignment percentage identity (default: 90)

  • --min_cov_vir
    Minimum alignment percentage coverage (default: 80)

All hits with 80–90% identity or 40–80% coverage are reported as spurious hits.

Virulence Score

A virulence score is calculated to categorize isolates based on a hierarchy of clinical severity and epidemic potential. The score reflects the highest-risk toxin detected.

Scoring criteria:

  • 4: PVL detected
  • 3: TSST-1 detected
  • 2: Exfoliative toxins detected
  • 1: Staphylococcal enterotoxins (SE) OR LukED detected
  • 0: No major accessory virulence factors detected

The following criteria also apply:

  • For lukFS and lukED both subunits must be found to contribute to the score

  • Genes reported in the truncated_virulence_hits and spurious_virulence_hits columns do not contribute to the virulence score.

  • Only the "most relevant" gene is considered, the cumulative presence of multiple genes do not contribute to the score.

Output

Results are reported as follows:

Field Description
vir_score Virulence score (0–4)
vir_pvl Detection of Panton-Valentine Leukocidin (Positive, Partial, or -)
vir_tsst Detected Toxic Shock Syndrome Toxin genes
vir_et Detected exfoliative toxin genes
vir_lukED Detection of Leukocidin ED (Positive, Partial, or -)
vir_se Detected Staphylococcal enterotoxin genes
truncated_virulence_hits Genes with truncations or premature stop codons
spurious_virulence_hits Genes with weak hits

List of genes

Gene Accession^ Citation^^
etA AAA17490 Sakurai et al. 1988
etB WP_010994026 Lee at al. 1987
etD QNW86327.1 Caban et al. 2020
etE AUG74510.1 Le Marechal et al. 2011
lukD WP_000782464; WP_000782469; YP_500453; WP_000782463 Gravet et al. 1998
lukE WP_000473596; WP_000473600; YP_500454; WP_000473593 Gravet et al. 1998
lukF WP_024937002 Kaneko et al. 1997; Badarau et al 2017
lukS WP_000239545 Kaneko et al. 1997; Badarau et al 2017
sea WP_000750406; WP_000750412 Betley et al. 1988
sec WP_001043550; WP_000278088; WP_001043551 Bohach et al. 1987; Chen et al. 2001
seh WP_000608674 Nilsson et al. 1999
sell WP_000746599; WP_000746597 Baba et al. 2008
selk WP_000733775; WP_000733771; WP_000734020 -
selq WP_001033316;WP_001033320; WP_001033321 McClure et al. 2018
tsst-1 WP_001035599; WP_001035596 Blomster-Hautamaa et al. 1986

Note:
^ One accession per variant is incuded.
^^ The citation is the one provided at the accession page