Extracellular proteases of Staphylococcus epidermidis: roles as virulence factors and their participation in biofilm

Martínez‐García, Sergio; Rodríguez‐Martínez, Sandra; Cancino-Diaz, Mario E.; Cancino‐Díaz, Juan C.

doi:10.1111/apm.12805

Cited by 44 publications

(30 citation statements)

References 42 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In vitro experiments revealed a very broad activity of both enzymes on the destruction of connective tissue, the evasion of host immunity and the modulation of biofilm integrity [51–57]. A staphopain A-like protease with similar functions, called EcpA, is also expressed by S. epidermidis and other coagulase-negative staphylococci [42, 58, 59]. In contrast, orthologues of the ssp ABC operon have only been identified in S. warneri [60, 61].…”

Section: Introductionmentioning

confidence: 99%

IntracellularStaphylococcus aureusemploys the cysteine protease staphopain A to induce host cell death in epithelial cells

Stelzner

Hertlein

Sroka

et al. 2020

Preprint

View full text Add to dashboard Cite

Staphylococcus aureus is a major human pathogen, which can invade and survive in non-professional and professional phagocytes. Intracellularity is thought to contribute to pathogenicity and persistence of the bacterium. Upon internalization by epithelial cells, cytotoxic S. aureus strains can escape from the phagosome, replicate in the cytosol and induce host cell death. Here, we identified a staphylococcal cysteine protease to induce cell death by intracellular S. aureus after translocation into the host cell cytoplasm. We demonstrated that loss of staphopain A function leads to delayed onset of host cell death and prolonged intracellular replication of S. aureus in epithelial cells. Overexpression of staphopain A in a non-cytotoxic strain facilitated intracellular killing of the host cell even in the absence of detectable intracellular replication. Moreover, staphopain A contributed to efficient colonization of the lung in a mouse pneumonia model. Our study suggests that staphopain A is utilized by S. aureus to mediate escape from the host cell and thus contributes to tissue destruction and dissemination of infection. Author Summary Staphylococcus aureus is a well-known antibiotic-resistant pathogen that emerges in hospital and community settings and can cause a variety of diseases ranging from skin abscesses to lung inflammation and blood poisoning. The bacterium asymptomatically colonizes the upper respiratory tract and skin of about one third of the human population and takes advantage of opportune conditions, like immunodeficiency or breached barriers, to cause infection. Although S. aureus is not regarded as a professional intracellular bacterium, it can be internalized by human cells and subsequently exit the host cells by induction of cell death, which is considered to cause tissue destruction and spread of infection. The bacterial virulence factors and underlying molecular mechanisms involved in the intracellular lifestyle of S. aureus remain largely unknown. We identified a bacterial cysteine protease to contribute to host cell death mediated by intracellular S. aureus. Staphopain A induced killing of the host cell after translocation of the pathogen into the cell cytosol, while bacterial proliferation was not required. Further, the protease enhanced survival of the pathogen during lung infection. These findings reveal a novel, intracellular role for the bacterial protease staphopain A.

show abstract

Section: Introductionmentioning

confidence: 99%

IntracellularStaphylococcus aureusemploys the cysteine protease staphopain A to induce host cell death in epithelial cells

Stelzner

Hertlein

Sroka

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Additionally, studies have observed the role of these bacterially secreted proteases in influencing polymicrobial dynamics. Previous investigations have shown that in competition for nasal mucosa between Staphylococcus aureus and Staphylococcus epidermidis, S. epidermidis strains that produce the serine protease Esp are able to outcompete and eradicate nasal colonization of S. aureus (32,33).…”

Section: Introductionmentioning

confidence: 99%

The Streptococcal Protease SpeB Antagonizes the Biofilms of the Human PathogenStaphylococcus aureusUSA300 through Cleavage of the Staphylococcal SdrC Protein

et al. 2020

View full text Add to dashboard Cite

Streptococcus pyogenes, or group A Streptococcus (GAS), is both a pathogen and an asymptomatic colonizer of human hosts and produces a large number of surface-expressed and secreted factors that contribute to a variety of infection outcomes. The GAS-secreted cysteine protease SpeB has been well studied for its effects on the human host; however, despite its broad proteolytic activity, studies on how this factor is utilized in polymicrobial environments are lacking. Here, we utilized various forms of SpeB protease to evaluate its antimicrobial and antibiofilm properties against the clinically important human colonizer Staphylococcus aureus, which occupies niches similar to those of GAS. For our investigation, we used a skin-tropic GAS strain, AP53CovS+, and its isogenic ΔspeB mutant to compare the production and activity of native SpeB protease. We also generated active and inactive forms of recombinant purified SpeB for functional studies. We demonstrate that SpeB exhibits potent biofilm disruption activity at multiple stages of S. aureus biofilm formation. We hypothesized that the surface-expressed adhesin SdrC in S. aureus was cleaved by SpeB, which contributed to the observed biofilm disruption. Indeed, we found that SpeB cleaved recombinant SdrC in vitro and in the context of the full S. aureus biofilm. Our results suggest an understudied role for the broadly proteolytic SpeB as an important factor for GAS colonization and competition with other microorganisms in its niche. IMPORTANCE Streptococcus pyogenes (GAS) causes a range of diseases in humans, ranging from mild to severe, and produces many virulence factors in order to be a successful pathogen. One factor produced by many GAS strains is the protease SpeB, which has been studied for its ability to cleave and degrade human proteins, an important factor in GAS pathogenesis. An understudied aspect of SpeB is the manner in which its broad proteolytic activity affects other microorganisms that co-occupy niches similar to that of GAS. The significance of the research reported herein is the demonstration that SpeB can degrade the biofilms of the human pathogen Staphylococcus aureus, which has important implications for how SpeB may be utilized by GAS to successfully compete in a polymicrobial environment.

show abstract

“…Additionally, the proteases of the species Stenotrophomonas maltophilia, Pseudomonas putida, Klebsiella oxytoca, and Pantoea dispersa, identified in this work as proteases producers (Table 1), have already been characterized (Tondo et al, 2004;Nicodème et al, 2005;Gohel et al, 2007;Ribitsch et al, 2012). With respect to the genera Burkholderia, Staphylococcus, and Ochrobactrum, the proteases of the species Burkholderia pseudomallei, Staphylococcus aureus, Staphylococcus epidermidis, and Ochrobactrum anthropi were also characterized (Bompard-Gilles et al, 2000;Shaw et al, 2004;Chin et al, 2007;Martínez-García et al, 2018). Despite the production of proteases by the genera Isoptericola, Massilia, and Sphingomonas being also described in the literature (Lindquist et al, 2003;Willsey & Wargo, 2015, Bibi et al, 2017, none has been studied so far, and this is the first report about the species Staphylococcus hominis and Massilia timonae as protease producers (Table 1).…”

Section: Discussionmentioning

confidence: 70%

Research Article Isolation, diversity, and biotechnological potential of maize (Zea mays) grains bacteria

Santos¹,

Castro²,

Apolonio³

et al. 2019

Genet. Mol. Res.

View full text Add to dashboard Cite

F.C. Santos et al. 2 were chosen to be molecularly identified by DNA barcoding. A phylogenetic tree showed that most of the bacterial strains belonged to the phylum Proteobacteria, but some also were from the phyla Actinobacteria and Firmicutes. Some of the isolated species had already well-characterized enzymes. However, new producers were also found, including amylase producing isolate of Massilia timonae and a lipase producing isolate of Pantoea dispersa.

show abstract

Extracellular proteases of Staphylococcus epidermidis: roles as virulence factors and their participation in biofilm

Cited by 44 publications

References 42 publications

IntracellularStaphylococcus aureusemploys the cysteine protease staphopain A to induce host cell death in epithelial cells

IntracellularStaphylococcus aureusemploys the cysteine protease staphopain A to induce host cell death in epithelial cells

The Streptococcal Protease SpeB Antagonizes the Biofilms of the Human PathogenStaphylococcus aureusUSA300 through Cleavage of the Staphylococcal SdrC Protein

Research Article Isolation, diversity, and biotechnological potential of maize (<i>Zea</i> <i>mays</i>) grains bacteria

Contact Info

Product

Resources

About