Dataset Information

The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in Staphylococcus aureus.

ABSTRACT: Biofilm causes hospital-associated infections on indwelling medical devices. In Staphylococcus aureus, Biofilm formation is controlled by intricately coordinated network of regulating systems, of which the ATP-dependent protease ClpP shows an inhibitory effect. Here, we demonstrate that the inhibitory effect of ClpP on biofilm formation is through Agr and the cell wall hydrolase Sle1. Biofilm formed by clpP mutant consists of proteins and extracellular DNA (eDNA). The increase of the protein was, at least in part, due to the reduced protease activity of the mutant, which was caused by the decreased activity of agr. On the other hand, the increase of eDNA was due to increased cell lysis caused by the higher level of Sle1. Indeed, as compared with wild type, the clpP mutant excreted an increased level of eDNA, and showed higher sensitivity to Triton-induced autolysis. The deletion of sle1 in the clpP mutant decreased the biofilm formation, the level of eDNA, and the Triton-induced autolysis to wild-type levels. Despite the increased biofilm formation capability, however, the clpP mutant showed significantly reduced virulence in a murine model of subcutaneous foreign body infection, indicating that the increased biofilm formation capability cannot compensate for the intrinsic functions of ClpP during infection.

SUBMITTER: Liu Q

PROVIDER: S-EPMC5430930 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in Staphylococcus aureus.

Liu Qian Q Wang Xing X Qin Juanxiu J Cheng Sen S Yeo Won-Sik WS He Lei L Ma Xiaowei X Liu Xiaoyun X Li Min M Bae Taeok T

Frontiers in cellular and infection microbiology 20170515

Biofilm causes hospital-associated infections on indwelling medical devices. In Staphylococcus aureus, Biofilm formation is controlled by intricately coordinated network of regulating systems, of which the ATP-dependent protease ClpP shows an inhibitory effect. Here, we demonstrate that the inhibitory effect of ClpP on biofilm formation is through Agr and the cell wall hydrolase Sle1. Biofilm formed by clpP mutant consists of proteins and extracellular DNA (eDNA). The increase of t ...[more]

PMID: 28555174

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Project description:Biofilm development significantly enhances the virulence of methicillin-resistant Staphylococcus aureus (MRSA), leading to severe infections and decreased susceptibility to antibiotics, especially in strains associated with hospital environments. This study examined the occurrence of MRSA, their ability to form biofilms, agr typing, and the antibiotic resistance profiles of biofilm-forming MRSA strains isolated from environmental surfaces at Mymensingh Medical College Hospital (MMCH). From 120 swab samples, 86 (71.67%) tested positive for S. aureus. MRSA was identified in 86 isolates using the disk diffusion technique, and by polymerase chain reaction (PCR), 56 (65.1%) isolates were confirmed to carry the mecA gene. The Crystal Violet Microtiter Plate (CVMP) test revealed that 80.35% (45 isolates) were biofilm-forming and 19.6% (11 isolates) were non-biofilm-forming. Out of 45 biofilm producer isolates 37.5% and 42.9% isolates exhibited strong and intermediate biofilm-forming characteristics, respectively. Molecular analysis revealed that 17.78% of MRSA isolates carried at least one gene related to biofilm formation, specifically icaA, icaB, and icaD genes were discovered in 13.33%, 8.89%, 6.67% of the MRSA isolates, respectively. In agr typing, the most prevalent group was agr I (71.11%), followed by group III (17.78%) and group II (11.11%). Group IV was not detected. The distribution of agr gene groups showed a significant difference among biofilm-forming isolates (p < 0.05). In agr group I, 18.75% of isolates carried the icaA gene, 12.5% carried the icaB gene, and 9.37% carried the icaD gene. Biofilm-forming genes were not detected in any of the isolates from agr groups II or III. There are no statistically significant differences between agr groups and the presence of these genes (p > 0.05). Antibiotic resistance varied significantly among agr groups, with agr group I displaying the highest resistance, agr group II, and agr group III exhibiting the least resistance (p < 0.05). Seventy-three (73.3%) of the isolates were multi-drug resistant, with agr group I displaying nineteen MDR patterns. The occurrence of MRSA in hospital environments and their capacity to form biofilm raises concerns for public health. These findings support the importance of further research focused on agr quorum sensing systems as a basis for developing novel antibacterial agents.

Project description:Staphylococcus aureus biofilms are implicated in hospital infections due to elevated antibiotic and host immune system resistance. Molecular components of cell wall including amyloid proteins, peptidoglycans (PGs), and lipoteichoic acid (LTA) are crucial for biofilm formation and tolerance of methicillin-resistant S. aureus (MRSA). Significance of alkaline phosphatases (ALPs) for biofilm formation has been recorded. Serrapeptase (SPT), a protease of Serratia marcescens, possesses antimicrobial properties similar or superior to those of many antibiotics. In the present study, SPT anti-biofilm activity was demonstrated against S. aureus (ATCC 25923, methicillin-susceptible strain, methicillin-susceptible S. aureus (MSSA)) and MRSA (ST80), with IC50 values of 0.67 μg/mL and 7.70 μg/mL, respectively. SPT affected bacterial viability, causing a maximum inhibition of - 46% and - 27%, respectively. Decreased PGs content at [SPT] ≥ 0.5 μg/mL and ≥ 8 μg/mL was verified for MSSA and MRSA, respectively. In MSSA, LTA levels decreased significantly (up to - 40%) at lower SPT doses but increased at the highest dose of 2 μg/mL, a counter to spectacularly increased cellular and secreted LTA levels in MRSA. SPT also reduced amyloids of both strains. Additionally, intracellular ALP activity decreased in both MSSA and MRSA (up to - 85% and - 89%, respectively), while extracellular activity increased up to + 482% in MSSA and + 267% in MRSA. Altered levels of DING proteins, which are involved in phosphate metabolism, in SPT-treated bacteria, were also demonstrated here, implying impaired phosphorus homeostasis. The differential alterations in the studied molecular aspects underline the differences between MSSA and MRSA and offer new insights in the treatment of resistant bacterial biofilms. KEY POINTS: • SPT inhibits biofilm formation in methicillin-resistant and methicillin-susceptible S. aureus. • SPT treatment decreases bacterial viability, ALP activity, and cell wall composition. • SPT-treated bacteria present altered levels of phosphate-related DING proteins.

Dataset Information

The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in Staphylococcus aureus.

Publications

The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in <i>Staphylococcus aureus</i>.

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