scholarly journals Inhibition of the ATP Synthase Eliminates the Intrinsic Resistance of Staphylococcus aureus towards Polymyxins

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Martin Vestergaard ◽  
Katrine Nøhr-Meldgaard ◽  
Martin Saxtorph Bojer ◽  
Christina Krogsgård Nielsen ◽  
Rikke Louise Meyer ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atp Synthase ◽  
Bacterial Infections ◽  
Polymyxin B ◽  
Important Class ◽  
Intrinsic Resistance ◽  
Gram Positive ◽  
Gram Negative ◽  
Bacterial Diseases ◽  
Development Of Resistance

ABSTRACT Staphylococcus aureus is intrinsically resistant to polymyxins (polymyxin B and colistin), an important class of cationic antimicrobial peptides used in treatment of Gram-negative bacterial infections. To understand the mechanisms underlying intrinsic polymyxin resistance in S. aureus, we screened the Nebraska Transposon Mutant Library established in S. aureus strain JE2 for increased susceptibility to polymyxin B. Nineteen mutants displayed at least 2-fold reductions in MIC, while the greatest reductions (8-fold) were observed for mutants with inactivation of either graS, graR, vraF, or vraG or the subunits of the ATP synthase (atpA, atpB, atpG, or atpH), which during respiration is the main source of energy. Inactivation of atpA also conferred hypersusceptibility to colistin and the aminoglycoside gentamicin, whereas susceptibilities to nisin, gallidermin, bacitracin, vancomycin, ciprofloxacin, linezolid, daptomycin, and oxacillin were unchanged. ATP synthase activity is known to be inhibited by oligomycin A, and the presence of this compound increased polymyxin B-mediated killing of S. aureus. Our results demonstrate that the ATP synthase contributes to intrinsic resistance of S. aureus towards polymyxins and that inhibition of the ATP synthase sensitizes S. aureus to this group of compounds. These findings show that by modulation of bacterial metabolism, new classes of antibiotics may show efficacy against pathogens towards which they were previously considered inapplicable. In light of the need for new treatment options for infections with serious pathogens like S. aureus, this approach may pave the way for novel applications of existing antibiotics. IMPORTANCE Bacterial pathogens that cause disease in humans remain a serious threat to public health, and antibiotics are still our primary weapon in treating bacterial diseases. The ability to eradicate bacterial infections is critically challenged by development of resistance to all clinically available antibiotics. Polymyxins constitute an important class of antibiotics for treatment of infections caused by Gram-negative pathogens, whereas Gram-positive bacteria remain largely insusceptible towards class of antibiotics. Here we performed a whole-genome screen among nonessential genes for polymyxin intrinsic resistance determinants in Staphylococcus aureus. We found that the ATP synthase is important for polymyxin susceptibility and that inhibition of the ATP synthase sensitizes S. aureus towards polymyxins. Our study provides novel insights into the mechanisms that limit polymyxin activity against S. aureus and provides valuable targets for inhibitors to potentially enable the use of polymyxins against S. aureus and other Gram-positive pathogens. IMPORTANCE Bacterial pathogens that cause disease in humans remain a serious threat to public health, and antibiotics are still our primary weapon in treating bacterial diseases. The ability to eradicate bacterial infections is critically challenged by development of resistance to all clinically available antibiotics. Polymyxins constitute an important class of antibiotics for treatment of infections caused by Gram-negative pathogens, whereas Gram-positive bacteria remain largely insusceptible towards this class of antibiotics. Here we performed a whole-genome screen among nonessential genes for polymyxin intrinsic resistance determinants in Staphylococcus aureus. We found that the ATP synthase is important for polymyxin susceptibility and that inhibition of the ATP synthase sensitizes S. aureus towards polymyxins. Our study provides novel insights into the mechanisms that limit polymyxin activity against S. aureus and provides valuable targets for inhibitors to potentially enable the use of polymyxins against S. aureus and other Gram-positive pathogens.

scholarly journals Affectivity of Zatoria multiflora Boiss extracts Against Bacteria

2011 ◽  
Vol 46 (1) ◽  
pp. 105-110
Author(s):  
M Ur Rahman ◽  
S Gul ◽  
EA Odhano ◽  
Ir Hafeez ◽  
RB Tareen
Keyword(s):  
Staphylococcus Aureus ◽  
Methanol Extract ◽  
Inhibitory Effect ◽  
Bacterial Strains ◽  
It Use ◽  
Gram Positive ◽  
Reference Drug ◽  
Gram Negative ◽  
Bacterial Diseases ◽  
Gram Positive Bacteria

The extracts of Zatoria multiflora Boiss were evaluated for prospective antibacterial activity against gram negative and gram positive bacteria. Cefoperazone is used as antibacterial reference drug. The activity of ethanol and methanol extract varied from organism to organism. The inhibitory effect of both the extracts and their 50/50 combination was more pronounced against gram positive bacteria. The MIC and MBC values were in the range of 1.718-6.25 and 2.832-6.25 mg/ml respectively. Significant (p=0.05) synergistic effect of combination of EtOH and MeOH extracts was recorded against Staphylococcus aureus ATCC 29213, Staphylococcus aureus ATCC 25923 while additive effect against rest of the bacterial strains. The present studies provide evidences for presence of antibacterial elements in alcoholic extracts and recommends for more exploration for it use against bacterial diseases. Key words: Extracts; Zatoria multiflora Boiss; Antibacterial; MIC; MBC; Synergistic. DOI: http://dx.doi.org/10.3329/bjsir.v46i1.3652 Bangladesh J. Sci. Ind. Res. 46(1), 105-110, 2011

scholarly journals Antibacterial Effect of Carbosilane Metallodendrimers in Planktonic Cells of Gram-Positive and Gram-Negative Bacteria and Staphylococcus aureus Biofilm

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 405 ◽  
Author(s):  
Celia Llamazares ◽  
Natalia Sanz del Olmo ◽  
Paula Ortega ◽  
Rafael Gómez ◽  
Juan Soliveri ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
First Generation ◽  
Antibacterial Effect ◽  
Resistance Mechanism ◽  
Planktonic Cells ◽  
Gram Positive ◽  
Health Security ◽  
Gram Negative ◽  
Escherichia Coli Bacteria

Antibiotic resistance is currently one of the main threats to public health security. Biofilm formation is a resistance mechanism that is responsible for most human bacterial infections and requires new and effective therapeutic approaches, such as those provided by nanotechnology. In this work, the antibacterial effect of carbosilane metallodendrimers with different metals (copper(II) and ruthenium(II)), ligands (chloride and nitrate) and generations (generation 0, 1 and 2) has been studied using planktonic Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Furthermore, the ability of the metallodendrimers to avoid the formation of S. aureus biofilms was also evaluated. The results showed a promising biocide activity in both types of planktonic bacteria, especially for first-generation dendrimers, which arises from the metal complexation to the dendrimer. Cu(II) metallodendrimers require lower concentration than Ru(II) counterpart to inhibit the production of S. aureus biofilms, but none produce hemolysis at the inhibitory concentrations and can be safely used as antibacterial agents. In particular, the first-generation Cu(II) metallodendrimer with nitrate ligands displayed the most promising properties to continue with further studies in both planktonic cells and biofilms.

scholarly journals P006 MICROBIOLOGY OF CHRONIC MESH INFECTION

2021 ◽  
Vol 108 (Supplement_8) ◽  
Author(s):  
Claudio Birolini ◽  
Mario Paulo Faro ◽  
Eduardo Tanaka ◽  
Jocielle Miranda ◽  
Edivaldo Utiyama
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Positive Culture ◽  
Complete Removal ◽  
Resistant Bacteria ◽  
Mesh Infection ◽  
Gram Positive ◽  
Acinetobacter Baumanii ◽  
Gram Negative ◽  
Mesh Placement

Abstract Aim Mesh infection represents a significant concern due to its terrible consequences. Mesh sinus, infected seromas, mesh extrusion, and mesh-related enteric fistulas are common complications associated with synthetic mesh. This study aimed to review the microbiota of mesh infection in a series of 100 patients submitted to mesh explantation. Material and Methods We reviewed the charts of patients presenting with a history of mesh infection lasting six months or more after mesh placement. All patients submitted to further abdominal wall repair with complete removal of the infected mesh and presenting a positive culture were included. The microbiota analysis was based on positive cultures obtained from the fluids and tissues surrounding the mesh or a positive culture of the mesh itself. Microorganisms were divided into gram-positive or gram-negative, aerobic or anaerobic, and fungi. Results Pure aerobic gram-positive cultures were encountered in 50% of the patients, followed by a combination of aerobic gram-positive/gram-negative (9%) and pure gram-negative cultures (6%). Anaerobes were recovered from 31% of patients. Fungi were recovered from 6%. Staphylococcus aureus was identified in 64% of cultures, with methicillin-resistant Staphylococcus aureus present in 42% and methicillin-sensitive Staphylococcus aureus in 22%. Among aerobic gram-negative infections, six (17%) were caused by multi-resistant bacteria, including Pseudomonas aeruginosa, Proteus mirabilis, Acinetobacter baumanii, Klebsiella pneumoniae complex, and Enterobacter cloacae complex. Conclusions Pure Staphylococcus aureus infections, occurring in 29%, accounted for most single bacterial infections. Gram-negative infections and anaerobes were commonly encountered in polymicrobial infections. Most fungi cultures occurred in patients with enteric fistulas.

Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

2021 ◽  
Author(s):  
Byungji Kim ◽  
Qinglin Yang ◽  
Leslie W. Chan ◽  
Sangeeta N. Bhatia ◽  
Erkki Ruoslahti ◽  
...  
Keyword(s):  
Porous Silicon ◽  
Broad Spectrum ◽  
Therapeutic Efficacy ◽  
Bacterial Infections ◽  
Silicon Nanoparticles ◽  
First Line ◽  
Gram Positive ◽  
Gram Negative ◽  
Porous Silicon Nanoparticles

RNAi-mediated immunotherapy provided by fusogenic porous silicon nanoparticles demonstrates superior therapeutic efficacy against both Gram-positive and Gram-negative bacterial infections compared with first-line antibiotics.

scholarly journals 1554. Epidemiology of Adult Bacterial Hand Infections at Two Urban Hospitals

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S777-S778
Author(s):  
Arsheena Yassin ◽  
Christine Stavropoulos ◽  
Krystina L Woods ◽  
Jiashan Xu ◽  
Justin Carale ◽  
...  
Keyword(s):  
New York ◽  
Staphylococcus Aureus ◽  
Antibiotic Regimen ◽  
Gram Positive ◽  
Gram Negative ◽  
Streptococcus Species ◽  
Urban Hospitals ◽  
Haemophilus Parainfluenzae ◽  
Empiric Antibiotic ◽  
Gram Negative Organisms

Abstract Background Hand infections represent a major source of morbidity, which can result in hand stiffness and amputation. Early appropriate empiric antibiotic regimen may reduce the associated morbidity, hence the importance to examine local epidemiology. The aim of this study was to define the current epidemiology of adult hand infections at two urban hospitals in New York City. Methods We performed a double center, retrospective study of adult patients hospitalized from March 2018 to May 2020. Patients with positive cultures associated with the hand infections were included. Retrospectively, 100 patients were reviewed. Data on baseline demographic, clinical, surgical, microbiology, and treatment parameters were collected. Results Of the 100 patients, 76% were male, with median age of 47.5 years (35, 58.25) and average C-reactive protein (CRP) of 50.66 mg/L (± 64.64) on admission (see Table 1). Previous hospitalization within 1 year (38%), previous surgical procedures (39%) and recent IV medication use (26%) were common. 130 bacterial isolates were identified (see Table 2). The most frequent organisms were Gram-positive, with Methicillin susceptible Staphylococcus aureus (MSSA, 25.38%), Streptococcus species (20.08%), and Methicillin resistant Staphylococcus aureus (MRSA, 15.38%) being the most common. Gram-negative organisms were infrequent, with Haemophilus parainfluenzae (3.85%), Enterobacter cloacae (3.85) and Pseudomonas aeruginosa (3.08%) being the most prevalent. Of the 100 patients, 27% had polymicrobial infections, associated with trauma (6%), illicit IV use (6%) and unknown (7%) etiologies. Table 1: Baseline demographics and co-morbid conditions Table 2: Types and numbers of organisms in relation to etiologies Conclusion Within our population, the most common organisms associated with hand infections were Gram-positive, with Staphylococcus aureus and Streptococcus species being the most prevalent. Gram-negative pathogens were infrequently isolated. The results within this study can provide guidance to clinicians on assessing the appropriate empiric antibiotic regimen in patients with hand infections, and can serve as a basis for further studies identifying risk factors associated with isolation of organisms associated with hand infections. Disclosures All Authors: No reported disclosures

scholarly journals Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 82
Author(s):  
Liping Liu ◽  
Hanne Ingmer ◽  
Martin Vestergaard
Keyword(s):  
Staphylococcus Aureus ◽  
Stress Response ◽  
Inhibitory Activity ◽  
Bacterial Species ◽  
Dna Integrity ◽  
Intrinsic Resistance ◽  
Potential Health ◽  
Cellular Effects ◽  
Development Of Resistance ◽  
Wide Range

Resveratrol has been extensively studied due to its potential health benefits in multiple diseases, for example, cancer, obesity and cardiovascular diseases. Besides these properties, resveratrol displays inhibitory activity against a wide range of bacterial species; however, the cellular effects of resveratrol in bacteria remain incompletely understood, especially in the human pathogen, Staphylococcus aureus. In this study, we aimed to identify intrinsic resistance genes that aid S. aureus in tolerating the activity of resveratrol. We screened the Nebraska Transposon Mutant Library, consisting of 1920 mutants with inactivation of non-essential genes in S. aureus JE2, for increased susceptibly to resveratrol. On agar plates containing 0.5× the minimum inhibitory concentration (MIC), 17 transposon mutants failed to grow. Of these, four mutants showed a two-fold reduction in MIC, being the clpP protease mutant and three mutants with deficiencies in the electron transport chain (menD, hemB, aroC). The remaining 13 mutants did not show a reduction in MIC, but were confirmed by spot-assays to have increased susceptibility to resveratrol. Several genes were associated with DNA damage repair (recJ, xerC and xseA). Treatment of S. aureus JE2 with sub-inhibitory concentrations of resveratrol did not affect the expression of recJ, xerC and xseA, but increased expression of the SOS–stress response genes lexA and recA, suggesting that resveratrol interferes with DNA integrity in S. aureus. Expression of error-prone DNA polymerases are part of the SOS–stress response and we could show that sub-inhibitory concentrations of resveratrol increased overall mutation frequency as measured by formation of rifampicin resistant mutants. Our data show that DNA repair systems are important determinants aiding S. aureus to overcome the inhibitory activity of resveratrol. Activation of the SOS response by resveratrol could potentially facilitate the development of resistance towards conventional antibiotics in S. aureus.

Bactericidal activity of disinfectants

2020 ◽  
pp. 13-18
Author(s):  
S. B. Lysko ◽  
M. V. Zadorozhnaya ◽  
O. A. Suntsova
Keyword(s):  
Federal State ◽  
Gram Positive ◽  
Gram Negative ◽  
Development Of Resistance ◽  
Wide Range ◽  
Ammonium Compounds ◽  
C Center ◽  
Test Cultures ◽  
Poultry Farming

The modern market of drugs off ers a wide range of disinfectants. However, the constant use of the same drugs contributes to the development of resistance in the microfl ora and reduces the quality of activities. In this regard to develop eff ective measures to combat and prevent infectious diseases, it is necessary to periodically monitor the activity of disinfectants used in the enterprise. The purpose of the researches was to study the bactericidal eff ect of disinfectants on the microfl ora of poultry enterprises. The researches have been carried out at the Siberian Scientifi c and Research Institute of Poultry Farming – a branch of the Federal State Budgetary Scientifi c Institution “Omsk Agrarian Scientifi c Center”. The activity of 8 disinfectants to 37 test cultures isolated from poultry farms of diff erent productivity trends and species of poultry (chickens, turkeys, quails) has been tested. It has been found as a result of the conducted research that the most expressed bactericidal eff ect on gram-positive and gram-negative microorganisms were complex disinfectants, which included glutaraldehyde in combination with quaternary ammonium compounds. Thus, 1 % solutions of Gludesive and Viroshield provided the death of all test cultures, Dinovis Ultra and TN-4+ – 92 and 84 % of cultures. The disinfecting activity of Mirosan drug and formalin was most expressed for gram-positive microfl ora, among gram-negative microfl ora resistance was registered in 25–75 % and 25–50 % of cultures, respectively. Drugs EcoSide Advansa and Ecocide C have showed the lowest activity to all investigated microorganisms. The largest number of resistant cultures to the tested disinfectants have been registered in the bacteria of the genus Citrobacter spp. and Pseudomonas aeruginosa, while simultaneously noted resistance to 4–6 drugs.

scholarly journals Antimicrobial Activity of Gardenia jasminoides Callus and Crude Leaf Extracts for some Organic Solvents against some Pathogenic Bacteria and Yeasts

2014 ◽  
Vol 8 (3) ◽  
pp. 40-45
Author(s):  
Zina Hashem Shehab ◽  
Huda Suhail Abid ◽  
Sumaya Fadhil Hamad ◽  
Sara Haitham
Keyword(s):  
Staphylococcus Aureus ◽  
Candida Albicans ◽  
Pathogenic Bacteria ◽  
Saccharomyces Boulardii ◽  
Gram Negative Bacteria ◽  
Proteus Vulgaris ◽  
Gram Positive ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Gardenia Jasminoides

The study was conducted to evaluate the inhibitory activity of methanol extract of Gardenia jasminoides leaves compared with leaf crude extracts for some organic solvents namely Methanol, Ethanol, Petroleum ether, Asetone and Chloroform on growth of some pathogenic bacteria and yeast, which included four gram positive isolates Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes and Bacillus cereus and gram negative isolates Escherichia coli, Salmonella typhi, Proteus vulgaris and Pseudomonas aeruginosa and some yeasts Candida albicans and Saccharomyces boulardii, by using well diffusion method. The inhibitory activity of extracts in the tested bacterial strains and yeasts was varied according to the type of extracting solvents and are tested microorganisms. The methanol callus extract which grown on Murashige and Skoog (MS) media by using (Naphthalen acitic acid) NAA and (Benzyle adenine) BA as growth regulator highly effective as compared to the other extracts as for inhibition of three gram positive bacteria and three gram negative bacteria,which include Staphylococcus aureus and, Proteus vulgaris, followed by acetone and ethanolic extracts which include two gram positive bacteria and two gram negative bacteria. All extracts had highly effect in growth of Candida albicans while all crude extracts didn’t show any sensitivity against Saccharomyces boulardii, and when we’d done (High Performance Liquid Chromatography) HPLC test for detection of some active compound we found Quinic acid, Iridiods glycosides and Crocin which its rate in fresh callus was higher than fresh leaves.

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