ABSTRACT
The efflux systems are considered important mechanisms of bacterial resistance due to their ability to extrude various antibiotics. Several naturally occurring compounds, such as sesquiterpenes, have demonstrated antibacterial activity and the ability to inhibit efflux pumps in resistant strains. Therefore, the objective of this research was to analyze the antibacterial and inhibitory activity of the efflux systems NorA, Tet(K), MsrA, and MepA by sesquiterpenes nerolidol, farnesol, and α-bisabolol, used either individually or in liposomal nanoformulation, against multi-resistant Staphylococcus aureus strains. The methodology consisted of in vitro testing of the ability of sesquiterpenes to reduce the Minimum Inhibitory Concentration (MIC) and enhance the action of antibiotics and ethidium bromide (EtBr) in broth microdilution assays. The following strains were used: S. aureus 1199B carrying the NorA efflux pump, resistant to norfloxacin; IS-58 strain carrying Tet(K), resistant to tetracyclines; RN4220 carrying MsrA, conferring resistance to erythromycin. For the EtBr fluorescence measurement test, K2068 carrying MepA was used. It was observed the individual sesquiterpenes exhibited better antibacterial activity as well as efflux pump inhibition. Farnesol showed the lowest MIC of 16.5 µg/mL against the S. aureus RN4220 strain. Isolated nerolidol stood out for reducing the MIC of EtBr to 5 µg/mL in the 1199B strain, yielding better results than the positive control CCCP, indicating strong evidence of NorA inhibition. The liposome formulations did not show promising results, except for liposome/farnesol, which reduced the MIC of EtBr against 1199B and RN4220. Further research is needed to evaluate the mechanisms of action involved in the inhibition of resistance mechanisms by the tested compounds.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Sesquiterpenes , Farnesol/pharmacology , Staphylococcus aureus/metabolism , Methicillin-Resistant Staphylococcus aureus/metabolism , Liposomes , Multidrug Resistance-Associated Proteins , Anti-Bacterial Agents/pharmacology , Sesquiterpenes/pharmacology , Ethidium/pharmacology , Microbial Sensitivity Tests , Bacterial Proteins/metabolismABSTRACT
Cystic fibrosis (CF) is a genetic disease that results in dysfunction of the CF transmembrane conductance regulator (CFTR) protein, which is a chloride and bicarbonate channel expressed in the apical portion of epithelial cells of various organs. Dysfunction of that protein results in diverse clinical manifestations, primarily involving the respiratory and gastrointestinal systems, impairing quality of life and reducing life expectancy. Although CF is still an incurable pathology, the therapeutic and prognostic perspectives are now totally different and much more favorable. The purpose of these guidelines is to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of the pulmonary symptoms of CF in Brazil. Questions in the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) format were employed to address aspects related to the use of modulators of this protein (ivacaftor, lumacaftor+ivacaftor, and tezacaftor+ivacaftor), use of dornase alfa, eradication therapy and chronic suppression of Pseudomonas aeruginosa, and eradication of methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex. To formulate the PICO questions, a group of Brazilian specialists was assembled and a systematic review was carried out on the themes, with meta-analysis when applicable. The results obtained were analyzed in terms of the strength of the evidence compiled, the recommendations being devised by employing the GRADE approach. We believe that these guidelines represent a major advance to be incorporated into the approach to patients with CF, mainly aiming to favor the management of the disease, and could become an auxiliary tool in the definition of public policies related to CF.
Subject(s)
Cystic Fibrosis , Methicillin-Resistant Staphylococcus aureus , Humans , Brazil , Cystic Fibrosis/drug therapy , Cystic Fibrosis/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Methicillin-Resistant Staphylococcus aureus/metabolism , Mutation , Quality of LifeABSTRACT
Chalcones and their derivatives are substances of great interest for medicinal chemistry due to their antibacterial activities. As the bacterial resistance to clinically available antibiotics has become a worldwide public health problem, it is essential to search for compounds capable of reverting the bacterial resistance. As a possibility, the chalcone class could be an interesting answer to this problem. The chalcones (2E)-1-(4'-aminophenyl)-3-(phenyl)prop-2-en-1-one (APCHAL), and (2E)-1-(4'-aminophenyl)-3-(4-chlorophenyl)prop-2-en-1-one (ACLOPHENYL) were synthesized by the Claisen-Schmidt condensation and characterized by 1H and 13C nuclear magnetic resonance (NMR), Fourier-transform infrared (FT-IR), and mass spectrometry (MS), In addition, microbiological tests were performed to investigate the antibacterial activity, modulatory potential, and efflux pump inhibition against Staphylococcus aureus (S. aureus) multi-resistant strains. Regarding the S. aureus Gram-positive model, the APCHAL presented synergism with gentamicin and antagonism with penicillin. APCHAL reduced the Minimum inhibitory concentration (MIC) of gentamicin by almost 70%. When comparing the effects of the antibiotic modifying activity of ACLOPHENYL and APCHAL, a loss of synergism is noted with gentamicin due to the addition of a chlorine to the substance structure. For Escherichia coli (E. coli) a total lack of effect, synergistic or antagonistic, was observed between ACLOPHENYL and the antibiotics. In the evaluation of inhibition of the efflux pump, both chalcones presented a synergistic effect with norfloxacin and ciprofloxacin against S. aureus, although the effect is much less pronounced with ACLOPHENYL. The effect of APCHAL is particularly notable against the K2068 (MepA overexpresser) strain, with synergistic effects with both ciprofloxacin and ethidium bromide. The docking results also show that both compounds bind to roughly the same region of the binding site of 1199B (NorA overexpresser), and that this region overlaps with the preferred binding region of norfloxacin. The APCHAL chalcone may contribute to the prevention or treatment of infectious diseases caused by multidrug-resistant S. aureus.
Subject(s)
Chalcone , Chalcones , Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Chalcones/pharmacology , Escherichia coli/metabolism , Methicillin-Resistant Staphylococcus aureus/metabolism , Microbial Sensitivity Tests , Multidrug Resistance-Associated Proteins , Spectroscopy, Fourier Transform Infrared , Staphylococcus aureus/metabolismABSTRACT
In methicillin-resistant Staphylococcus aureus (MRSA) treatment, the vancomycin minimum inhibitory concentration (MIC) increase, vancomycin heteroresistance (hVISA) presence, and accessory gene regulator (agr) dysfunction are predictors of vancomycin therapy failure. This study evaluated the association between vancomycin MIC (≥ 1.0 µg/mL) and agr dysfunction in invasive MRSA isolates. Vancomycin MIC, hVISA phenotype, agr group, and function were determined in 171 MRSA isolates obtained between 2014 and 2019 from hospitals in Porto Alegre, Brazil. All MRSA were susceptible to vancomycin; 16.4% of these had MIC ≥ 1.0 µg/mL. Seventeen MRSA isolates expressed the hVISA phenotype; 35.3% of them had MIC of 1.5 µg/mL. agr groups I (40.9%) and II (47.1%) were the most found groups for MRSA and hVISA isolates, respectively. The proportion of MRSA with vancomycin MIC ≥ 1.0 µg/mL in agr group II was significantly higher than in agr groups I and III (p = 0.002). agr dysfunction was observed in 4.7% (8/171) of MRSA, especially those with vancomycin MIC ≥ 1.0 µg/mL (p < 0.001). In addition, six isolates (35.3%; 6/17) with hVISA phenotype presented agr dysfunction, which was significantly higher than that in non-hVISA phenotype (p < 0.001). In conclusion, agr dysfunction in MRSA is associated with vancomycin MIC ≥ 1.0 µg/mL and hVISA phenotype, which suggests that agr dysfunction might confer potential advantages on MRSA to survive in invasive infections.
Subject(s)
Bacterial Proteins/metabolism , Methicillin-Resistant Staphylococcus aureus/drug effects , Trans-Activators/metabolism , Vancomycin/pharmacology , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Brazil , Humans , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/metabolism , Microbial Sensitivity Tests , Phenotype , Staphylococcal Infections/microbiology , Trans-Activators/genetics , Vancomycin Resistance/drug effectsABSTRACT
AIMS: Staphylococcus aureus is one of the most common pathogens in hospital environment and community. Panton-Valentine leukocidin (PVL) production is clinically associated with skin abscesses, soft tissues infections, bacteraemia and sepsis. This study aimed to investigate the effects of the presence of genes lukF/S-PV coding for PVL, in histological and haematological features during systemic infection, using a Swiss mice experimental model. METHODS AND RESULTS: Experiments were performed using 25 mice distributed into five experimental groups, intravenously inoculated with 50 µl suspensions at density 1·0 × 107 CFU per ml of strains: methicillin-susceptible (MSSA) and pvl-negative strains isolated from nasal colonization; MSSA pvl-positive strains isolated from nasal colonization; methicillin-resistant (MRSA) and pvl-positive strains isolated from peripheral blood of a patient with severe pulmonary infection; and a MRSA pvl-positive strains isolated from a peripheral blood culture of a patient with bacteraemia. Haematological analysis was performed at 24, 48, 72 and 96 h post-infection. Morphoanatomy and histopathological analyses were performed at 96 h post-infection. For all S. aureus strains tested, the capability of intravenous dissemination and survival into mice tissues was demonstrated. Inflammatory processes at different levels were related to the presence of pvl genes, and included alterations in the format, size and colour of the organs. Staphylococcus aureus pvl-positive strains were detected in greater numbers in the organs of the infected animals. CONCLUSIONS: The pvl-positive strains isolated from blood cultures were capable to induce the greatest modifications in both haematological and histopathological profiles, and seemed to aggravate the systemic infections. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings are valuable in characterizing infections caused by S. aureus in humans and murine.
Subject(s)
Bacterial Toxins/metabolism , Exotoxins/metabolism , Leukocidins/metabolism , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Staphylococcal Infections/microbiology , Staphylococcal Infections/pathology , Animals , Bacteremia/microbiology , Bacteremia/pathology , Bacterial Toxins/genetics , Disease Models, Animal , Exotoxins/genetics , Humans , Leukocidins/genetics , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/growth & development , Methicillin-Resistant Staphylococcus aureus/metabolism , Mice , Staphylococcus aureus/genetics , Staphylococcus aureus/growth & development , Staphylococcus aureus/metabolism , Staphylococcus aureus/pathogenicityABSTRACT
We investigated the responses and mechanisms of action of methicillin-resistant Staphylococcus aureus (MRSA) metabolism when exposed under sublethal concentrations of the synergistic antibacterial combination of nisin + oxacillin (» of maximum sublethal concentration) and sublethal concentrations of oxacillin only and nisin only. A total of 135 proteins were identified, showing an alteration in the expression of 85 proteins when treatment was compared with untreated bacteria (control). When the bacteria were treated using the combination, there was an increase in the expression of proteins related to resistance (e.g., beta-lactamase) and also in the ones involved in protein synthesis, and there was a decrease in the expression of proteins related to stress and alterations in proteins related to bacterial energy metabolism. Bacterial oxidative stress showed that the combination was able to induce oxidative stress (p < 0.05) and increase enzyme activities and lipid hydroperoxide levels compared with individual treatments. The analysis of cell ultrastructure showed damage in MRSA, especially on the bacterial wall and the plasma membrane, with cell lysis and death. Thus, the changes caused by these treatments affected different proteins related to the bacterial biological processes and signaling pathways such as cell division, structure, stress, regulation, bacterial resistance, protein synthesis, gene expression, energetic metabolism, and virulence. It was observed that synergism among antimicrobials has high potential in therapeutic use and may reduce the required amounts of antibacterial substances in addition to being effective on different targets in bacterial cells.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Gene Expression Regulation, Bacterial , Methicillin-Resistant Staphylococcus aureus/drug effects , Nisin/pharmacology , Oxacillin/pharmacology , Bacterial Proteins/classification , Bacterial Proteins/metabolism , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Wall/drug effects , Cell Wall/metabolism , Drug Combinations , Drug Synergism , Energy Metabolism/drug effects , Energy Metabolism/genetics , Gene Ontology , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/metabolism , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Microbial Sensitivity Tests , Molecular Sequence Annotation , Oxidative Stress , Protein Biosynthesis/drug effects , Protein Biosynthesis/genetics , Proteomics/methods , Virulence/drug effects , beta-Lactamases/genetics , beta-Lactamases/metabolismABSTRACT
Foodborne diseases (FBD) occur worldwide and affect a large part of the population, being a cause of international concern among health authorities. Staphylococcus aureus can be transmitted by contaminated food, and it is one of the pathogens that most cause foodborne outbreaks in Brazil. Currently, this organism's ability in developing resistance to antibiotics is notorious; methicillin-resistant Staphylococcus aureus-MRSA-is known for its resistance to methicillin, oxacillin, and others. MRSA is one of the leading causes of infections, becoming a major threat to human health worldwide due to the numerous toxins that can produce. At first, the transmission of MRSA occurred in clinical environments; but in recent decades, its presence has been reported in the community, outside the hospital environment, including food and food-producing animals around the world. In this review, information about MRSA was gathered to verify MRSA incidence in the world but especially in Brazil in food samples, food handlers, food-producing animals, and food processing environments. The studies show that MRSA is easily found and in certain cases with high frequency, thus representing a potential risk to public health.
Subject(s)
Bacterial Proteins , Food Microbiology , Foodborne Diseases/microbiology , Methicillin-Resistant Staphylococcus aureus , Penicillin-Binding Proteins , Prevalence , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Brazil , Humans , Methicillin/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/metabolism , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Microbial Sensitivity Tests , Oxacillin/pharmacology , Penicillin-Binding Proteins/genetics , Penicillin-Binding Proteins/metabolism , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Staphylococcus aureus/metabolism , Staphylococcus aureus/pathogenicityABSTRACT
Staphylococcus aureus is the most prominent cause of skin and soft tissue infections (SSTI) worldwide. Mortality associated with invasive SSTI is a major threat to public health considering the incidence of antibiotic resistant isolates in particular methicillin resistant S. aureus both in the hospital (HA-MRSA) and in the community (CA-MRSA). To overcome the increasing difficulties in the clinical management of SSTI due to MRSA, new prophylactic and therapeutic approaches are urgently needed and a preventive vaccine would be welcome. The rational design of an anti-S. aureus vaccine requires a deep knowledge of the role that the different bacterial virulence factors play according to the type of infection. In the present study, using a set of isogenic deficient mutants and their complemented strains we determined that the staphylococcal surface proteins SpA and Sbi play an important role in the induction of inflammatory cytokines and chemokines in the skin during SSTI. SpA and Sbi initiate signaling cascades that lead to the early recruitment of neutrophils, modulate their lifespan in the skin milieu and contribute to proper abscess formation and bacterial eradication. Moreover, the expression of SpA and Sbi appear critical for skin repair and wound healing. Thus, these results indicate that SpA and Sbi can promote immune responses in the skin that are beneficial for the host and therefore, should not be neutralized with vaccine formulations designed to prevent SSTI.
Subject(s)
Abscess/immunology , Antigens, Bacterial/metabolism , Bacterial Proteins/metabolism , Carrier Proteins/metabolism , Skin/immunology , Soft Tissue Infections/metabolism , Staphylococcal Infections/metabolism , Staphylococcus aureus/metabolism , Wound Healing/physiology , Abscess/metabolism , Abscess/microbiology , Animals , Chemokines/metabolism , Cytokines/metabolism , Disease Models, Animal , Humans , Keratinocytes , Methicillin-Resistant Staphylococcus aureus/metabolism , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Skin/microbiology , Skin/pathology , Soft Tissue Infections/immunology , Soft Tissue Infections/microbiology , Soft Tissue Infections/pathology , Staphylococcal Infections/immunology , Staphylococcus aureus/pathogenicityABSTRACT
Marine natural product drug discovery has begun to play an important role in the treatment of disease, with several recently approved drugs. In addition, numerous microbial natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces, due to their metabolic diversity for production of biologically active secondary metabolites. However, many secondary metabolites cannot be produced under laboratory conditions because growth conditions in flask culture differ from conditions in the natural environment. Various experimental conditions (e.g., mixed fermentation) have been attempted to increase yields of previously described metabolites, cause production of previously undetected metabolites, and increase antibiotic activity. Adult ascidians-also known as tunicates-are sessile marine invertebrates, making them vulnerable to predation and therefore are hypothesized to use host-associated bacteria that produce biologically active secondary metabolites for chemical defense. A marine-derived Streptomyces sp. strain PTY087I2 was isolated from a Panamanian tunicate and subsequently co-cultured with human pathogens including Bacillus subtilis, methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa, followed by extraction. Co-culture of Streptomyces sp. PTY087I2 with each of these human pathogens resulted in increased production of three antibiotics: granaticin, granatomycin D, and dihydrogranaticin B, as well as several analogues seen via molecular networking. In addition, co-cultures resulted in strongly enhanced biological activity against the Gram positive human pathogens used in these experiments. Expanded utilization of co-culture experiments to allow for competitive interactions may enhance metabolite production and further our understanding of these microbial interactions.
Subject(s)
Anti-Bacterial Agents/pharmacology , Hydrocarbons, Cyclic/isolation & purification , Streptomyces/chemistry , Animals , Anti-Bacterial Agents/isolation & purification , Coculture Techniques , Humans , Marine Biology , Methicillin-Resistant Staphylococcus aureus/metabolism , Microbial Sensitivity Tests , Naphthoquinones/isolation & purification , Panama , Pseudomonas aeruginosa/metabolism , Up-Regulation/drug effects , Urochordata/microbiologyABSTRACT
BACKGROUND: Staphylococcus aureus is characterized by its pathogenicity and high prevalence, causing disease in both healthy and immunocompromised individuals due to its easy dissemination. This fact is aggravated by the widespread dissemination of S. aureus carrying toxigenic genes. The objective of this study was to determine the toxigenic profile of methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in patients with purulent skin and/or soft tissue infections seen at the Dermatology Department of the University Hospital of the Botucatu Medical School, asymptomatic adults older than 60 years living in nursing homes, and prison inmates of the Avaré Detention Center. METHODS: PCR was used for the detection of the mecA gene, enterotoxin genes (sea, seb, and sec), exfoliative toxins A and B (eta and etb), toxic shock syndrome toxin 1 (tst), panton-valentine leukocidin (lukS-PV and lukF-PV), and alpha- and delta-hemolysins or cytotoxins (hla and hld). RESULTS: The results showed a significant prevalence of toxigenic genes among S. aureus isolates from asymptomatic individuals, with the observation of a higher prevalence of cytotoxin genes. However, the panton-valentine leukocidin gene was only detected in MSSA isolated from patients with skin infections and the tst gene was exclusively found in MSSA isolated from prison inmates. CONCLUSIONS: The present study demonstrated a significant prevalence of toxigenic genes in MSSA and MRSA strains isolated from asymptomatic S. aureus carriers. There was a higher prevalence of cytotoxin genes.
Subject(s)
Bacterial Toxins/genetics , Methicillin-Resistant Staphylococcus aureus/metabolism , Methicillin/pharmacology , Staphylococcal Infections/microbiology , Staphylococcus aureus/metabolism , Aged , Bacterial Toxins/metabolism , Female , Humans , Male , Methicillin Resistance , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Prisoners/statistics & numerical data , Staphylococcus aureus/drug effects , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purificationABSTRACT
This study was conducted to determine the species distribution, antimicrobial resistance pheno- and genotypes and virulence traits of mannitol-positive methicillin-resistant staphylococci (MRS) isolated from pigs in Nsukka agricultural zone, Nigeria. Twenty mannitol-positive methicillin-resistant coagulase-negative staphylococcal (MRCoNS) strains harboring the mecA gene were detected among the 64 Staphylococcus isolates from 291 pigs. A total of 4 species were identified among the MRCoNS isolates, namely, Staphylococcus sciuri (10 strains), Staphylococcus lentus (6 strains), Staphylococcus cohnii (3 strains) and Staphylococcus haemolyticus (one strain). All MRCoNS isolates were multidrug-resistant. In addition to ß-lactams, the strains were resistant to fusidic acid (85%), tetracycline (75%), streptomycin (65%), ciprofloxacin (65%), and trimethoprim/sulphamethoxazole (60%). In addition to the mecA and blaZ genes, other antimicrobial resistance genes detected were tet(K), tet(M), tet(L), erm(B), erm(C), aacA-aphD, aphA3, str, dfrK, dfrG, cat pC221, and cat pC223. Thirteen isolates were found to be ciprofloxacin-resistant, and all harbored a Ser84Leu mutation within the QRDR of the GyrA protein, with 3 isolates showing 2 extra substitutions, Ser98Ile and Arg100Lys (one strain) and Glu88Asp and Asp96Thr (2 strains). A phylogenetic tree of the QRDR nucleotide sequences in the gyrA gene revealed a high nucleotide diversity, with several major clusters not associated with the bacterial species. Our study highlights the possibility of transfer of mecA and other antimicrobial resistance genes from MRCoNS to pathogenic bacteria, which is a serious public health and veterinary concern.
Subject(s)
Drug Resistance, Multiple, Bacterial/genetics , Fermentation/physiology , Mannitol/metabolism , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/metabolism , Staphylococcus haemolyticus/isolation & purification , Staphylococcus haemolyticus/metabolism , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , DNA Gyrase/genetics , DNA, Bacterial/genetics , Genes, Bacterial/genetics , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Microbial Sensitivity Tests , Nigeria , Penicillin-Binding Proteins/genetics , Staphylococcal Infections/microbiology , Staphylococcus haemolyticus/genetics , Staphylococcus haemolyticus/pathogenicity , Swine/microbiologyABSTRACT
This study was conducted to determine the species distribution, antimicrobial resistance pheno- and genotypes and virulence traits of mannitol-positive methicillin-resistant staphylococci (MRS) isolated from pigs in Nsukka agricultural zone, Nigeria. Twenty mannitol-positive methicillin-resistant coagulase-negative staphylococcal (MRCoNS) strains harboring the
Subject(s)
Animals , Drug Resistance, Multiple, Bacterial/genetics , Fermentation/physiology , Mannitol/metabolism , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/metabolism , Staphylococcus haemolyticus/isolation & purification , Staphylococcus haemolyticus/metabolism , Anti-Bacterial Agents/pharmacology , DNA Gyrase/genetics , DNA, Bacterial/genetics , Genes, Bacterial/genetics , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Microbial Sensitivity Tests , Nigeria , Staphylococcal Infections/microbiology , Staphylococcus haemolyticus/genetics , Staphylococcus haemolyticus/pathogenicity , Swine/microbiologyABSTRACT
This study was conducted to determine the species distribution, antimicrobial resistance pheno- and genotypes and virulence traits of mannitol-positive methicillin-resistant staphylococci (MRS) isolated from pigs in Nsukka agricultural zone, Nigeria. Twenty mannitol-positive methicillin-resistant coagulase-negative staphylococcal (MRCoNS) strains harboring the
Subject(s)
Animals , Drug Resistance, Multiple, Bacterial/genetics , Fermentation/physiology , Mannitol/metabolism , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/metabolism , Staphylococcus haemolyticus/isolation & purification , Staphylococcus haemolyticus/metabolism , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/genetics , DNA Gyrase/genetics , DNA, Bacterial/genetics , Genes, Bacterial/genetics , Microbial Sensitivity Tests , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Nigeria , Penicillin-Binding Proteins/genetics , Staphylococcal Infections/microbiology , Staphylococcus haemolyticus/genetics , Staphylococcus haemolyticus/pathogenicity , Swine/microbiologyABSTRACT
The isolation of mannitol-negative methicillin-resistant Staphylococcus aureus from nasal swabs is reported. Among the 59 isolates, 9 (15%) isolates were mannitol-negative; all of these isolates were categorized as staphylococcal cassette chromosome mec (SCCmec) type IVa. This report emphasizes that mannitol fermentation on mannitol salt agar should not be used as the sole criterion when screening nasal swab specimens for S. aureus.
Subject(s)
Mannitol/metabolism , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/metabolism , Nasal Mucosa/microbiology , Brazil , DNA, Bacterial/genetics , Fermentation , Genetic Loci , Humans , Methicillin-Resistant Staphylococcus aureus/classificationABSTRACT
Bacterial infections represent one of the main threats to global public health. One of the major causative agents associated with high morbidity and mortality infections in hospitals worldwide is methicillin-resistant Staphylococcus aureus. Therefore, there is a need to develop new antibacterial agents to treat these infections, and natural products are a rich source of them. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin, isolated and characterized from Larrea tridentate, showed the best activity towards methicillin-resistant S. aureus. Thus, the aim of this study was to determine the potential molecular mechanism of the antibacterial activity of 3'-demethoxy-6-O-demethylisoguaiacin against methicillin-resistant S. aureus using microarray technology. Results of microarray genome expression were validated by real-time polymerase chain reaction (RT-PCR). The genetic profile expression results showed that lignan 3'-demethoxy-6-O-demethylisoguaiacin had activity on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This molecular mechanism is not present in any antibacterial commercial drug and could be a new target for the development of novel antibacterial agents.
Subject(s)
ATP-Binding Cassette Transporters/antagonists & inhibitors , Anti-Bacterial Agents/pharmacology , Bacterial Proteins/antagonists & inhibitors , Gene Expression Regulation, Bacterial , Larrea/chemistry , Lignans/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Naphthols/pharmacology , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/isolation & purification , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Cell Membrane/chemistry , Cell Membrane/drug effects , Gene Expression Profiling , Lignans/chemistry , Lignans/isolation & purification , Methicillin-Resistant Staphylococcus aureus/genetics , Methicillin-Resistant Staphylococcus aureus/growth & development , Methicillin-Resistant Staphylococcus aureus/metabolism , Microbial Sensitivity Tests , Naphthols/chemistry , Naphthols/isolation & purification , Oligonucleotide Array Sequence Analysis , Plant Leaves/chemistry , Real-Time Polymerase Chain ReactionABSTRACT
The isolation of mannitol-negative methicillin-resistant Staphylococcus aureus from nasal swabs is reported. Among the 59 isolates, 9 (15%) isolates were mannitol-negative; all of these isolates were categorized as staphylococcal cassette chromosome mec (SCCmec) type IVa. This report emphasizes that mannitol fermentation on mannitol salt agar should not be used as the sole criterion when screening nasal swab specimens for S. aureus.(AU)
Subject(s)
Humans , Mannitol/metabolism , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/metabolism , Nasal Mucosa/microbiology , Brazil , DNA, Bacterial/genetics , Fermentation , Genetic Loci , Methicillin-Resistant Staphylococcus aureus/classificationABSTRACT
The isolation of mannitol-negative methicillin-resistant Staphylococcus aureus from nasal swabs is reported. Among the 59 isolates, 9 (15%) isolates were mannitol-negative; all of these isolates were categorized as staphylococcal cassette chromosome mec (SCCmec) type IVa. This report emphasizes that mannitol fermentation on mannitol salt agar should not be used as the sole criterion when screening nasal swab specimens for S. aureus.
Subject(s)
Humans , Mannitol/metabolism , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/metabolism , Nasal Mucosa/microbiology , Brazil , DNA, Bacterial/genetics , Fermentation , Genetic Loci , Methicillin-Resistant Staphylococcus aureus/classificationABSTRACT
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of both nosocomial and community-acquired infections. We describe an outbreak caused by the MRSA Pediatric clone expressing an unusual lincosamide resistant phenotype. Between January and May 2006, an MRSA outbreak was detected at the Neonatal Unit of Hospital Interzonal General de Agudos "Evita", Buenos Aires Province, Argentina that affected ten patients. Seven isolates from seven patients plus five MRSA recovered from health care workers (nasal carriage) were studied. Two phenotypes were observed: (i) ELCi (10), resistance to erythromycin and lincomycin and inducible resistance to clindamycin; (ii) ELiCi (2), resistance to erythromycin and inducible resistance to lincomycin and clindamycin. All 12 MRSA were resistant to oxacillin, erythromycin and gentamicin. Isolates expressing the ELCi-phenotype showed lincomycin MIC values between 16 and 32mg/L, while the remaining 2 isolates with ELiCi-phenotype presented a MIC value of 0.5mg/L. No differences were observed between the clindamycin MIC values in both phenotypes, ranging 0.25-0.5mg/L. Isolates showing ELCi-phenotype harbored ermC plus lnuA genes, and the other two only ermC gene. All 12 isolates were genetically related and belonged to the Pediatric clone (ST100) harboring a new variant of SCCmecIV. This is the first MRSA outbreak expressing an unusual ELCi phenotype due to a combination of ermC plus lnuA genes.
Subject(s)
Bacterial Proteins/metabolism , Cross Infection/epidemiology , Methicillin-Resistant Staphylococcus aureus/metabolism , Staphylococcal Infections/transmission , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , Cross Infection/drug therapy , Cross Infection/microbiology , Cross Infection/transmission , Disease Outbreaks , Drug Resistance, Multiple, Bacterial/drug effects , Genetic Variation , Humans , Infant, Newborn , Infectious Disease Transmission, Patient-to-Professional , Intensive Care Units, Neonatal , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Microbial Sensitivity Tests , Patient Care Team , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiologyABSTRACT
BACKGROUND AND AIMS: Staphylococcus aureus is a principal cause of human bacterial infection worldwide. The dissemination of antibiotic resistance among S. aureus strains is very import in the treatment of Staphylococcal infections. We undertook this study to identify methicillin-resistant Staphylococcus aureus (MRSA) clones responsible for nosocomial infection in five medical centers in Monterrey, Nuevo León (N.L.), México from 2005-2009. METHODS: One hundred ninety MRSA strains collected from 2005-2009 from five hospitals affiliated with the Instituto Mexicano del Seguro Social (IMSS) in Monterrey, N.L., México were characterized by antimicrobial susceptibility, pulsed field gel electrophoresis (PFGE) and Staphylococcal Cassette Chromosome mec (SCCmec) typing. RESULTS: Only one clone was present in the five hospitals (clone C); this clone is strongly associated with the New York-Japan clone (SCCmec II) with a broad resistance profile. CONCLUSIONS: This study clearly documented the high ability for dissemination and the persistence of the New York-Japan clone in these centers.
Subject(s)
Cross Infection/epidemiology , Methicillin Resistance , Methicillin-Resistant Staphylococcus aureus/classification , Staphylococcal Infections/epidemiology , Cross Infection/microbiology , Electrophoresis, Gel, Pulsed-Field , Hospitals , Humans , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Methicillin-Resistant Staphylococcus aureus/metabolism , Mexico , Phylogeny , Staphylococcal Infections/microbiologyABSTRACT
Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) may represent a serious public health problem, owing to the spread of toxin-producing lineages. The presence of genes encoding for Panton-Valentine leukocidin (PVL) is an important virulence marker, as the clinical sequelae of PVL-positive infections are often described as more severe than those of PVL-negative S. aureus infections. To date, the presence of PVL has not appeared to be common in Italy; we describe the intrafamilial transmission of an epidemic PVL-producing CA-MRSA lineage, Southwest Pacific clone (SWP). Our data suggested that the strain circulated from the father, who was recurrently affected by a soft tissue infection, to the mother, who showed nasal colonization, and to their child, who was hospitalized with symptoms of necrotizing pneumonia. In this case, we found that a recurrent skin infection that is not normally taken into account may represent a serious threat if caused by a PVL-producing strain. Our findings may have considerable implications for strategies for infection control and treatment of methicillin-resistant S. aureus infections.