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Staphylococcus aureus β-hemolysin causes skin inflammation by acting as an agonist of epidermal growth factor receptor.

ABSTRACT:

Importance

Staphylococcus aureus is a Gram-positive opportunistic bacterium that is responsible for the majority of skin infections in humans. Our study provides important molecular insights into the pathogenesis of S. aureus skin infections and identifies a potential therapeutic target for the treatment of these infections. Our findings also indicate that β-hemolysin (Hlb) secreted by colonized S. aureus is a risk factor for epidermal growth factor receptor (EGFR)-related diseases by acting as an agonist of EGFR. The neutralized monoclonal antibody we have developed for the first time will provide a functional inhibitor of Hlb. This study provides important insights to better understand the relationship between the skin colonization of S. aureus and inflammatory skin diseases.

SUBMITTER: Jia Y

PROVIDER: S-EPMC10783061 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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<i>Staphylococcus aureus</i> β-hemolysin causes skin inflammation by acting as an agonist of epidermal growth factor receptor.

Jia Yonggen Y Guan Zhangchun Z Liu Chenghua C Huang Minjun M Li Jingjing J Feng Jiannan J Shen Beifen B Yang Guang G

Microbiology spectrum 20231207 1

<h4>Importance</h4><i>Staphylococcus aureus</i> is a Gram-positive opportunistic bacterium that is responsible for the majority of skin infections in humans. Our study provides important molecular insights into the pathogenesis of <i>S. aureus</i> skin infections and identifies a potential therapeutic target for the treatment of these infections. Our findings also indicate that β-hemolysin (Hlb) secreted by colonized <i>S. aureus</i> is a risk factor for epidermal growth factor receptor (EGFR)-r ...[more]

PMID: 38059627

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Project description:Staphylococcus aureus produces various hemolysins regulated by the Agr-QS system, except β-hemolysin encoded by the gene hlb. A classical laboratory S. aureus strain RN4220 displays only the β-hemolysin phenotype. It was suspected that the 8A mutation at the end of its agrA gene delayed the expressions of hla and RNAIII, then failed to express α- and δ-hemolysins. However, hla gene expression was detected at the later culture time without α-hemolysin phenotype, the reason for such a phenotype has not been clearly understood. We created hlb knockout and complementary mutants via homologous recombination in RN4220 and NRS049, two strains that normally produce β-hemolysin and carry agrA mutation. We found interestingly that the presence or absence of α-hemolysin phenotype in such strains depended on the expression of β-hemolysin instead of agrA mutations, which only inhibited δ-hemolysin expression. The hemolysis phenotype was verified by the Christie-Atkinson-Munch-Peterson (CAMP) test. Quantitative reverse transcription PCR was carried out to evaluate the relative gene expressions of hlb, hla, and RNAIII. The construction of mutants did not affect the agrA mutation status. We demonstrate that the absence of α-hemolysin in S. aureus RN4220 and NRS049 strains is attributed to their production of β-hemolysin instead of agrA mutation. Our findings broaden the understanding of the molecular mechanisms that control hemolysin expression in S. aureus that is crucial for the development of new therapeutic strategies to combat S. aureus infections.Importanceα-Hemolysin is a critical virulence factor in Staphylococcus aureus and its expression is largely controlled by the Agr-QS system. Nonetheless, the hemolysis phenotype and the regulation of the Agr-QS system in S. aureus still hold many mysteries. Our study finds that it is the expression of β- hemolysin rather than the agrA mutation that inhibits the function of the α-hemolysin in an important S. aureus strain RN4220 and a clinical strain presents a similar phenotype, which clarifies the misunderstood hemolytic phenotype and mechanism of S. aureus. Our findings highlight the interactions among different toxins and their biological roles, combined with QS system regulation, which is ultimately the true underlying cause of its virulence. This emphasizes the importance of considering the collaborative action of various factors in the infection process caused by this significant human pathogen.