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Effect of silver nanoparticles on vancomycin resistant Staphylococcus aureus infection in critically ill patients.

ABSTRACT: A prevalent increase in antimicrobial resistance represents a universal obstacle for the treatment of Staphylococcus aureus (S. aureus) infection, especially in critically ill patients. Silver nanoparticles are defined as broad spectrum bactericidal agents, which might be effective against vancomycin resistant S. aureus (VRSA). In this study, we examined the bactericidal efficacy of silver nanoparticles on VRSA in 150 blood and sputum samples isolated from intensive care patients. Methicillin resistant S. aureus (MRSA) isolates were identified in 83 samples, with an incidence of 55.3%. Meanwhile, VRSA isolates were found in 11 and 8 isolates (a total of 19 isolates out of 150) from sputum and blood samples, with an incidence of 14.67% and 10.67%, respectively, with a total incidence of 12.67%. Vancomycin intermediate S. aureus (VISA) isolates had an inhibitory zone ranging from 9 to 13 mm, which was found in 13 out of 19 isolates, whereas VRSA isolates had an inhibitory zone ranging from 0 to 6 mm, which was detected in 6 out of 19 isolates. The findings of this study confirm that silver nanoparticles are an effective treatment against VRSA.

SUBMITTER: Elsawy S

PROVIDER: S-EPMC8547882 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Effect of silver nanoparticles on vancomycin resistant Staphylococcus aureus infection in critically ill patients.

Elsawy Saeid S Elsherif Walaa M WM Hamed Rasha R

Pathogens and global health 20210419 5

A prevalent increase in antimicrobial resistance represents a universal obstacle for the treatment of <i>Staphylococcus aureus (S. aureus)</i> infection, especially in critically ill patients. Silver nanoparticles are defined as broad spectrum bactericidal agents, which might be effective against vancomycin resistant <i>S. aureus</i> (VRSA). In this study, we examined the bactericidal efficacy of silver nanoparticles on VRSA in 150 blood and sputum samples isolated from intensive care patients. ...[more]

PMID: 33872131

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Project description:The emergence of pandrug-resistant (PDR) and extensive drug-resistant (XDR) methicillin-resistant and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) isolates from bovine milk samples along with biofilm formation ability and harboring various virulence genes complicates the treatment of bovine mastitis and highlights the serious threat to public health. This study investigated for the first time the frequency, antimicrobial resistance profiles, biofilm-forming ability, virulence factors, spa and staphylococcal cassette chromosome mec (SCCmec) types of MRSA and VRSA isolated from clinical and subclinical bovine mastitis in Egypt. A total of 808 milk samples were collected from each quarter of 202 dairy animals, including 31 buffaloes and 171 cattle. The frequency of mastitis in the collected milk samples was 48.4% (60/124) in buffaloes and 29.2% (200/684) in cattle. A total of 65 Staphylococcus species isolates were recovered, including 27 coagulase-positive S. aureus (CoPS) isolates and 38 coagulase-negative staphylococci (CoNS). The CoNS included 27 mammaliicocci (20 Mammaliicoccus lentus and 7 M. sciuri) and 11 Non-aureus staphylococci (S. lugdunensis) isolates. All the CoPS isolates were mecA positive and resistant to 20-33 tested antimicrobials with multiple antibiotic resistance index ranging from 0.61 to 1. Three isolates were PDR, four were XDR, and 20 were multidrug resistant isolates. VRSA was detected in 85.2% of CoPS isolates with minimal inhibitory concentration (MIC) ranging from 64 to 1024 µg/mL. The vanA gene was found in 60.8%, vanB in 73.9%, and both genes in 43.5% of VRSA isolates. All the CoPS isolates exhibited biofilm formation ability, with 55.6% being strong, and 44.4% moderate biofilm producers, and harbored icaA (74.1%) and icaD (74.1%) biofilm-forming genes. All S. aureus isolates harbored both beta-haemolysin (hlb) and leucotoxin (lukMF) genes, while 44.4% were positive for toxic shock syndrome toxin (tsst) gene. Enterotoxin genes sea, seb, sec, sed, and see were found in 59.3%, 40.7%, 18.5%, 33.3%, and 14.8% of isolates, respectively. Additionally, 70.4% of the isolates had spa X-region gene, and exhibited eight different MRSA spa types (t127, t267, t037, t011, t843, t1081, t2663, and t1575), with spa t127 being the most common. Three SCCmec types (I, II and III) were identified, with SCCmec I being predominant, and were further classified into subtypes 1.1.1, 1.1.2, 1.n.1, and 4.1.1. The ability of MRSA and VRSA isolates to produce biofilms and resist antimicrobials highlights the serious threat these pathogens pose to bovine milk safety, animal welfare, and public health. Therefore, strict hygiene practices and antimicrobial surveillance are crucial to reduce the risk of MRSA and VRSA colonization and dissemination.

Project description:Resistance to antibiotics is an increasing problem and necessitates novel antibacterial therapies. The polyketide antibiotics cervimycin A to D are natural products of Streptomyces tendae HKI 0179 with promising activity against multidrug-resistant staphylococci and vancomycin-resistant enterococci. To initiate mode of action studies, we selected cervimycin C- and D-resistant (CmR) Staphylococcus aureus strains. Genome sequencing of CmR mutants revealed amino acid exchanges in the essential histidine kinase WalK, the Clp protease proteolytic subunit ClpP or the Clp ATPase ClpC, and the heat shock protein DnaK. Interestingly, all characterized CmR mutants harbored a combination of mutations in walK and clpP or clpC. In vitro and in vivo analyses showed that the mutations in the Clp proteins abolished ClpP or ClpC activity, and the deletion of clpP rendered S. aureus but not all Bacillus subtilis strains cervimycin-resistant. The essential gene walK was the second mutational hotspot in the CmR S. aureus strains, which decreased WalK activity in vitro and generated a vancomycin-intermediate resistant phenotype, with a thickened cell wall, a lower growth rate, and reduced cell lysis. Transcriptomic and proteomic analyses revealed massive alterations in the CmR strains compared to the parent strain S. aureus SG511, with major shifts in the heat shock regulon, the metal ion homeostasis, and the carbohydrate metabolism. Taken together, mutations in the heat shock genes clpP, clpC, and dnaK, and the walK kinase gene in CmR mutants induced a vancomycin-intermediate resistant phenotype in S. aureus, suggesting cell wall metabolism or the Clp protease system as primary target of cervimycin. IMPORTANCE Staphylococcus aureus is a frequent cause of infections in both the community and hospital setting. Resistance development of S. aureus to various antibiotics is a severe problem for the treatment of this pathogen worldwide. New powerful antimicrobial agents against Gram-positives are needed, since antibiotics like vancomycin fail to cure vancomycin-intermediate resistant S. aureus (VISA) and vancomycin-resistant enterococci (VRE) infections. One candidate substance with promising activity against these organisms is cervimycin, which is an antibiotic complex with a yet unknown mode of action. In our study, we provide first insights into the mode of action of cervimycins. By characterizing cervimycin-resistant S. aureus strains, we revealed the Clp system and the essential kinase WalK as mutational hotspots for cervimycin resistance in S. aureus. It further emerged that cervimycin-resistant S. aureus strains show a VISA phenotype, indicating a role of cervimycin in perturbing the bacterial cell envelope.

Dataset Information

Effect of silver nanoparticles on vancomycin resistant Staphylococcus aureus infection in critically ill patients.

Publications

Effect of silver nanoparticles on vancomycin resistant Staphylococcus aureus infection in critically ill patients.

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