Table 1.
Summary of the known virulence factors of ESKAPE organisms.
| Process involved with virulence | Bacterial species | Associated molecule(s) | Role in pathogenesis | Gene(s) | Reference(s) |
|---|---|---|---|---|---|
| Adhesion | Enterococcus sp. | Enterococcal surface protein (ESP) | Enhances persistence in UTI | esp | (Toledo-Arana et al., 2001) |
| Aggregation substance | Facilitates donor–recipient contact during conjugation | asa1, asp1, and acs10 | (Rozdzinski et al., 2001; Sava et al., 2010) | ||
| MSCRAMMAce | Binds to collagen | ace, acm, and scm | (Hendrickx et al., 2009) | ||
| Capsule | Adheres to ECM | cpsF, cpsC, cpsD, cpsE cpsG, and cpsI | (Thurlow et al., 2009) | ||
| Staphylococcus aureus | MSCRAMMs | Protein that binds to collagen | ena, cna, ebps, and bbp | (Firoozeh et al., 2020) | |
| Fibronectin binding proteins A, B | Aids cell adhesion | fnbA, B | (Firoozeh et al., 2020) | ||
| Clumping factors, A and B | Facilitates the colonization of protein-coated biomaterials | clfA, B | (Firoozeh et al., 2020) | ||
| Klebsiella pneumoniae | Type I and III fimbriae | Facilitates adhesion | fimA, fimH, mrkA, and mrkD | (Alcántar-Curiel et al., 2013) | |
| Type VI protein secretion system | Aids cell invasion and in vivo colonization | icmF1 and icmF2 | (Hsieh et al., 2019) | ||
| Acinetobacter baumannii | Capsule | Facilitates cell–cell adhesion | pglC and ptk | (Murray et al., 2017) | |
| Pseudomonas aeruginosa | Type IV pili (TFP) | Facilitates adhesion | pilU | (Whitchurch and Mattick, 1994; Choy et al., 2008) | |
| Alginate | Enhances adhesion to solid surfaces | algC, algD, and algT | (Muhammadi and Ahmed, 2007) | ||
| Enterobacter sp. | Type VI secretion system | Aids cell adherence and facilitates colonization | clpV1 and clpV2 | (Soria-Bustos et al., 2020) | |
| Enterobactin | Improves adsorption to metal surfaces | entB | (Upritchard et al., 2011) | ||
| Ability to produce enzymes and toxins | Enterococcus sp. | Hemolysin | Cytolytic protein that cleaves the erythrocytes | EF_0700 | (Zhang et al., 2007) |
| Gelatinase | Cleaves gelatin, collagen, casein, hemoglobin, and other peptides | gelE | (Maasjost et al., 2019) | ||
| Hyaluronidase | Cleaves hyaluronate | hylEfm | (Maasjost et al., 2019) | ||
| Cytolysin | A two-peptide bacteriocin that forms pores | cylLL , cylL, cylM, cylB, and cylA | (Maasjost et al., 2019) | ||
| S. aureus | Hemolysins α, β, γ, and δ | Cleaves erythrocytes | hla, hlb, hld, and hlg | (Wang et al., 2014; Motamedi et al., 2018) | |
| Hyaluronidase | Enhanced intracellular survival and inhibition of pro inflammatory cytokine expression |
HysA | (Ibberson et al., 2014) | ||
| Collagenase | Cleaves collagen | yhbU_2 | (yhbU_2–collagenase-like protease–S. aureus–yhbU_2 gene and protein) | ||
| Panton-Valentine Leukocidin |
Forms pores |
lukS-PV
and lukF-PV |
(Melles et al., 2006) | ||
| Staphylokinase | Activates host plasminogen | sak | (Sako and Tsuchida, 1983) | ||
| K. pneumoniae | Hemolysin | Cleaves erythrocytes | hly | (Pereira and Vanetti, 2015; Esmaeel and Sadeq, 2018) | |
| Phospholipase D | Cleaves phospholipids |
pld1 | (Lery et al., 2014) | ||
| A. baumannii | Phospholipase (PLC and PLD) | Cleaves phospholipids | pld | (Lee et al., 2017; Murray et al., 2017) | |
| CipA | Binds to host plasminogen and can improve penetration into endothelial monolayers | cipA | (Koenigs et al., 2016) | ||
| P. aeruginosa | Enterotoxin | Forms pores in the cell membrane | tox A | (Pollack, 1984; Dapgh et al., 2019) | |
| Phospholipase | Cleaves phospholipids | pclH | (Dapgh et al., 2019) | ||
| Enterobacter sp. | Hemolysin | Cleaves erythrocytes | αhly | (Burgos, 2010) | |
| PrtA, B, and C family protease | Cleaves proteins | prtA, prtB, and prtC | (Ghigo and Wandersman, 1992) | ||
| Ability to evade the immune system | Enterococcus sp. | Capsule | Provides a barrier | cpsF, cpsC, cpsD, cpsE cpsG, and cpsI | (Thurlow et al., 2009) |
| S. aureus | Type 1 capsular polysaccharide | Provides a barrier | cap1 | (Luong et al., 2002) | |
| Clumping factor | Inhibits phagocytic engulfment | clfA, B | (Higgins et al., 2006) | ||
| Teichoic acid | Aids in disguise | tarB, tarD, tarF, tarIJ, and tarH | (D’Elia et al., 2006) | ||
| K. pneumoniae | Capsular polysaccharide-mediated factors | Provides a barrier | Cps | (Hsu et al., 2016) | |
| A. baumannii | Lipopolysaccharide (LPS) | Binds to the CD14/TLR4/MD2 receptor complex of immune cells | lpxA, lpxC, and lpxD | (Moffatt et al., 2013; Lee et al., 2017) | |
| Outer membrane protein A (OmpA), Omp33-36, and Omp22 | Modulates autophagy | OmpA, Omp33-36, and Omp 22 | (Rumbo et al., 2014) | ||
| P. aeruginosa | Alkaline protease | Cleaves proteins | aprA | (Iiyama et al., 2017) | |
| Elastase | Cleaves elastin | lasB | (Rust et al., 1996) | ||
| Enterobacter sp. | Peptidoglycan | Regulates the accessibility of pathogen-associated molecular patterns (PAMPs) | – | – | |
| Horizontal gene transfer | Enterococcus sp. | Pili | Facilitates conjugation | ebp, pila, and pilb | (Hendrickx et al., 2009) |
| S. aureus | Sortase A | Links surface proteins to peptidoglycan | Sau‐SrtA | (Khare and Narayana, 2017) | |
| K. pneumoniae | Pilin | Facilitates conjugation | ecpA, ecpR, and ecpB | (Alcántar-Curiel et al., 2013) | |
| A. baumannii | Type VI protein secretion system | Facilitates conjugation | tss and tag | – | |
| P. aeruginosa | Type IV pili | Facilitates conjugation | pilU | (Whitchurch and Mattick, 1994) | |
| Enterobacter sp. | – | – | - | – | |
| Iron acquisition system | Enterococcus sp. | Fur | Regulates the uptake of free iron and maintains iron homeostasis | Fur | (Latorre et al., 2018) |
| S. aureus | Siderophores, staphyloferrin A (SA), and staphyloferrin B (SB) | Acquires free iron | sbn sfa | – | |
| Hts, Sir transporters | Staphyloferrin uptake | sirA hts | (Beasley et al., 2011) | ||
| K. pneumoniae | Siderophores, aerobactin (iuc), and salmochelin (iro) | Acquires free iron | iuc and iro | – | |
| A. baumannii | Acinetobactin NfuA |
Acquires free iron | – | – | |
| P. aeruginosa | Siderophores pyoverdines, PVDI, PVDII, and PVDIII; FpvAI and FpvB |
Acquires free iron Outer membrane transporters |
fpv | (Hartney et al., 2013; Bonneau et al., 2020) | |
| Enterobacter sp. | Yersiniabactin | Acquires free iron | irp1, irp2, and fyuA | – | |
| Ability to form a biofilm | Enterococcus sp. | Capsule | Mediates cell–cell adhesion | cpsF, cpsC, cpsD, cpsE cpsG, and cpsI | (Thurlow et al., 2009) |
| Cell wall polysaccharide | Contributes to form the extracellular matrix | epa | (Hancock et al., 2014) | ||
| Aggregation substance | Increases surface hydrophobicity | asa1, asp1, and acs10 | (Rozdzinski et al., 2001; Sava et al., 2010) | ||
| S. aureus | Aggregation substance | Increases surface hydrophobicity | Asa1 | (Sussmuth et al., 2000) | |
| K. pneumoniae | Capsular polysaccharide | Mediates cell–cell adhesion | – | – | |
| Type III fimbriae | Maintains contact by promoting fimbrial adhesion | MrkA, MrkBC, MrkD, and MrkF | (Schroll et al., 2010; Johnson et al., 2011) | ||
| A. baumannii | Capsular polysaccharide | Helps in capsule polymerization and assembly which aids in biofilm formation | Ptk and epsA | (Russo et al., 2010) | |
| P. aeruginosa | Type IV pili | Maintains contact | pilU | (Whitchurch and Mattick, 1994) | |
| Enterobacter sp. | Capsule | Mediates cell–cell adhesion | – | – |
"-" denotes insufficient information.