scholarly journals Coagulase-Negative Staphylococcal Strain Prevents Staphylococcus aureus Colonization and Skin Infection by Blocking Quorum Sensing

2017 ◽  
Vol 22 (6) ◽  
pp. 746-756.e5 ◽  
Author(s):  
Alexandra E. Paharik ◽  
Corey P. Parlet ◽  
Nadjali Chung ◽  
Daniel A. Todd ◽  
Emilio I. Rodriguez ◽  
...  
mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Morgan L. Grundstad ◽  
Corey P. Parlet ◽  
Jakub M. Kwiecinski ◽  
Jeffrey S. Kavanaugh ◽  
Heidi A. Crosby ◽  
...  

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) infections impact all patient populations both in the community and in health care settings. Despite advances in our knowledge of MRSA virulence, little is known about the regulatory mechanisms of USA100 health care-associated MRSA isolates, which are the second most frequently identified MRSA isolates found in all infections. This work focused on the contribution of the USA100 agr type II quorum-sensing system to virulence and antibiotic resistance. From a MRSA strain collection, we selected 16 representative USA100 isolates, constructed mutants with Δagr mutations, and characterized selected strain pairs for virulence factor expression, murine skin infection, and antibiotic resistance. For each strain pair, hemolysis and extracellular protease expression were significantly greater in the wild-type (WT) strains than in the Δagr mutants. Similarly, mice challenged with the WT strains had larger areas of dermonecrosis and greater weight loss than those challenged with the Δagr mutants, demonstrating that the USA100 agr system regulates virulence. Although USA100 isolates exhibit a high level of antibiotic resistance, the WT and Δagr strain pairs showed no difference in MICs by MIC testing. However, in the presence of a sub-MIC of vancomycin, most of the USA100 Δagr mutants exhibited slower growth than the WT isolates, and a couple of the Δagr mutants also grew more slowly in the presence of a sub-MIC of cefoxitin. Altogether, our findings demonstrate that the USA100 agr system is a critical regulator of virulence, and it may have a contribution to the optimal survival of these MRSA strains in the presence of antibiotics. IMPORTANCE USA100 health care-associated MRSA isolates are highly antibiotic resistant and can cause invasive disease across all patient populations. Even though USA100 strains are some of the most frequently identified causes of infections, little is known about virulence regulation in these isolates. Our study demonstrates that the USA100 agr quorum-sensing system is important for the control of toxin and exoenzyme production and that the agr system has a key role in skin infection. In some USA100 isolates, the agr system is important for growth in the presence of low levels of antibiotics. Altogether, our findings demonstrate that the USA100 agr system is a critical regulator of virulence and that it may make a contribution to the optimal survival of these MRSA strains in the presence of antibiotics.


2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Zhen-Zhen Liu ◽  
Yong-Jun Yang ◽  
Feng-Hua Zhou ◽  
Ke Ma ◽  
Xiao-Qi Lin ◽  
...  

AbstractGasdermin D (GSDMD), a member of the gasdermin protein family, is a caspase substrate, and its cleavage is required for pyroptosis and IL-1β secretion. To date, the role and regulatory mechanism of GSDMD during cutaneous microbial infection remain unclear. Here, we showed that GSDMD protected against Staphylococcus aureus skin infection by suppressing Cxcl1–Cxcr2 signalling. GSDMD deficiency resulted in larger abscesses, more bacterial colonization, exacerbated skin damage, and increased inflammatory cell infiltration. Although GSDMD deficiency resulted in defective IL-1β production, the critical role of IL-1β was counteracted by the fact that Caspase-1/11 deficiency also resulted in less IL-1β production but did not aggravate disease severity during S. aureus skin infection. Interestingly, GSDMD-deficient mice had increased Cxcl1 secretion accompanied by increased recruitment of neutrophils, whereas Caspase-1/11-deficient mice presented similar levels of Cxcl1 and neutrophils as wild-type mice. Moreover, the absence of GSDMD promoted Cxcl1 secretion in bone marrow-derived macrophages induced by live, dead, or different strains of S. aureus. Corresponding to higher transcription and secretion of Cxcl1, enhanced NF-κB activation was shown in vitro and in vivo in the absence of GSDMD. Importantly, inhibiting the Cxcl1–Cxcr2 axis with a Cxcr2 inhibitor or anti-Cxcl1 blocking antibody rescued host defence defects in the GSDMD-deficient mice. Hence, these results revealed an important role of GSDMD in suppressing the Cxcl1–Cxcr2 axis to facilitate pathogen control and prevent tissue damage during cutaneous S. aureus infection.


Cell Reports ◽  
2021 ◽  
Vol 36 (4) ◽  
pp. 109462
Author(s):  
Jakub M. Kwiecinski ◽  
Rachel M. Kratofil ◽  
Corey P. Parlet ◽  
Bas G.J. Surewaard ◽  
Paul Kubes ◽  
...  

2001 ◽  
Vol 69 (3) ◽  
pp. 1957-1960 ◽  
Author(s):  
Michael Otto ◽  
Hartmut Echner ◽  
Wolfgang Voelter ◽  
Friedrich Götz

ABSTRACT Cross-inhibition by quorum-sensing pheromones betweenStaphylococcus aureus and Staphylococcus epidermidis was investigated using all known S. aureus agr pheromone subgroups. All S. aureus subgroups were sensitive towards the S. epidermidis pheromone, with the exception of the recently identified subgroup 4. The subgroup 4 pheromone was also the only S. aureus pheromone able to inhibit the S. epidermidis agr response. The close relation of subgroup 4 to subgroup 1 suggests that subgroup 4 might have evolved from subgroup 1 by mutation under the selective pressure of competition with S. epidermidis. The competition between S. aureus and S. epidermidis by means of quorum-sensing cross talk seems to be generally in favor of S. epidermidis, which might explain the predominance of S. epidermidis on the skin and in infections on indwelling medical devices.


Sign in / Sign up

Export Citation Format

Share Document