Antibiotic Effects on Methicillin-Resistant Staphylococcus aureus Cytoplasmic Peptidoglycan Intermediate Levels and Evidence for Potential Metabolite Level Regulatory Loops

Vemula, Harika; Ayon, Navid J.; Burton, Alloch; Gutheil, William G.

doi:10.1128/aac.02253-16

Cited by 18 publications

(18 citation statements)

References 43 publications

(44 reference statements)

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“…Bacteria have developed sophisticated mechanisms of drug resistance to ensure their survival. Resistance to antibiotics can be achieved through multiple biochemical pathways [13] that include modification [14] and destruction of antibiotic molecules [15], decreased antibiotic penetration or increased efflux [16][17][18], modification or complete replacement, or bypassing of target site [19,20]. The effects of various antibiotics on cytoplasmic peptidoglycan metabolite levels in MRSA were determined and metabolite levels were high in S. aureus [21].…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of Ocular Staphylococcus aureus to Antibiotics and Multipurpose Disinfecting Solutions

Afzal¹,

Vijay²,

Stapleton³

et al. 2021

Antibiotics

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Staphylococcus aureus is a frequent cause of ocular surface infections worldwide. Of these surface infections, those involving the cornea (microbial keratitis) are most sight-threatening. S. aureus can also cause conjunctivitis and contact lens-related non-infectious corneal infiltrative events (niCIE). The aim of this study was to determine the rates of resistance of S. aureus isolates to antibiotics and disinfecting solutions from these different ocular surface conditions. In total, 63 S. aureus strains from the USA and Australia were evaluated; 14 were from niCIE, 26 from conjunctivitis, and 23 from microbial keratitis (MK). The minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) of all the strains to ciprofloxacin, ceftazidime, oxacillin, gentamicin, vancomycin, chloramphenicol, azithromycin, and polymyxin B were determined. The MIC and MBC of the niCIE strains to contact lens multipurpose disinfectant solutions (MPDSs) was determined. All isolates were susceptible to vancomycin (100%). The susceptibility to other antibiotics decreased in the following order: gentamicin (98%), chloramphenicol (76%), oxacillin (74%), ciprofloxacin (46%), ceftazidime (11%), azithromycin (8%), and polymyxin B (8%). In total, 87% of all the isolates were multidrug resistant and 17% of the isolates from microbial keratitis were extensively drug resistant. The microbial keratitis strains from Australia were usually susceptible to ciprofloxacin (57% vs. 11%; p = 0.04) and oxacillin (93% vs. 11%; p = 0.02) compared to microbial keratitis isolates from the USA. Microbial keratitis isolates from the USA were less susceptible (55%) to chloramphenicol compared to conjunctivitis strains (95%; p = 0.01). Similarly, 75% of conjunctivitis strains from Australia were susceptible to chloramphenicol compared to 14% of microbial keratitis strains (p = 0.04). Most (93%) strains isolated from contact lens wearers were killed in 100% MPDS, except S. aureus 27. OPTI-FREE PureMoist was the most active MPDS against all strains with 35% of strains having an MIC ≤ 11.36%. There was a significant difference in susceptibility between OPTI-FREE PureMoist and Biotrue (p = 0.02). S. aureus non-infectious CIE strains were more susceptible to antibiotics than conjunctivitis strains and conjunctivitis strains were more susceptible than microbial keratitis strains. Microbial keratitis strains from Australia (isolated between 2006 and 2018) were more susceptible to antibiotics in comparison with microbial keratitis strains from the USA (isolated in 2004). Most of the strains were multidrug-resistant. There was variability in the susceptibility of contact lens isolates to MPDSs with one S. aureus strain, S. aureus 27, isolated from niCIE, in Australia in 1997 being highly resistant to all four MPDSs and three different types of antibiotics. Knowledge of the rates of resistance to antibiotics in different conditions and regions could help guide treatment of these diseases.

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Section: Introductionmentioning

confidence: 99%

Susceptibility of Ocular Staphylococcus aureus to Antibiotics and Multipurpose Disinfecting Solutions

Afzal¹,

Vijay²,

Stapleton³

et al. 2021

Antibiotics

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“…As a consequence, less lipid II has to be synthesized de novo , thus downregulating the transcription of the lipid II biosynthesis genes. As a result, only a limited amount of lipid II (1.5 x 10 5 lipid II molecules per cell (38)) is available for cell division and cell growth, explaining the significantly reduced growth of SansrFP -expressing cells compared to the control cells. A lower amount of lipid II molecules is further hampering the building of new PGNs (43).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of BceAB-type transporter: Resistance by lipid II flipping

Zaschke-Kriesche

Unsleber

Voitsekhovskaia

et al. 2020

Preprint

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Treatment of bacterial infections are the great challenge of our era due to the evolved resistance mechanisms against antibiotics. The Achilles heel of bacteria is the cell wall especially during the needs of its synthesis and cell division. Here lipid II is an essential cell wall precursor component synthesized in the cytosol and flipped into the outer leaflet of the membrane prior to its incorporation into the cell wall. Compounds targeting the cell wall or its biosynthesis precursors have been around for decades and have been used as antibiotics against bacterial infections like meningitis, pneumonia and endocarditis. Antimicrobial peptides (AMPs) have proven to be a promising weapon against multiresistant bacteria. However, the Bacitracin efflux (BceAB)-type ATP binding cassette transporters expressed in the membrane of human pathogenic bacteria have been shown to confer resistance to these alternative antibiotics, thereby hampering their medical development.In Streptococcus agalactiae COH1 the BceAB-type transporter NsrFP (SaNsrFP) confers highlevel resistance against the antimicrobial peptide nisin, a member of the lantibiotic subfamily. We showed that SaNsrFP provides a novel resistance mechanism by flipping lipid II back into the cytosol, thereby preventing the binding of nisin as well as other lipid II targeting compounds. This is intriguing since a relatively simple reaction mediates resistance to human pathogenic bacteria to lipid II targeting antibiotics, regardless of their structure. Significance StatementThe ABC-transporter NsrFP from Streptococcus agalactiae (SaNsrFP) belongs to the BceAB-type transporters. Several BceAB-type transporters are known to confer resistance against multiple antimicrobial peptides. In this study a new resistance mechanism was identified, which is based on the reduction of the number of cell wall precursor lipid II molecules on the cell surface mediated by SaNsrFP. SaNsrFP flips lipid II, which are considered to be the target for many antibiotics, back into the cytoplasm. With this newly gained knowledge about the resistance mechanism of BceAB-type transporters, novel strategies can be established to overcome or bypass this resistance in human pathogenic bacteria. Main Text

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“…The antibiotic inhibits the growth in vitro of Escherichia coli, Staphylococcus aureus, Enterococcus, Nocardia and Chlamydia species [25,26], Enterobacteriaceae [20] and other species of microorganisms. The minimum inhibitory concentration of D-cycloserine is 16-64 µg/ml for Escherichia coli, 64-128 µg/ml for grampositive bacteria Enterococcus faecium [27], 8-64 µg/ml for Staphylococcus aureus [27,28]. The minimum concentration of antibiotic that inhibits the growth of bacteria in relation to gram-negative Enterobacteriaceae is 2-100 µg/ml and more [24].…”

Section: Investigation Of Dynamics Of D-cycloserine Releasementioning

confidence: 99%

Study of Biodegradation of Film Materials with D-Cycloserine Based on Polyurethaneurea and the Dynamics of Drug Release

Rudenchyk¹,

Rozhnova²,

Galatenko³

et al. 2019

AJPST

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The study of the ability to biodegradation of film materials with D-cycloserine obtained on the basis of polyurethaneurea with fragments of the copolymer of N-vinylpyrrolidone with vinyl acetate and vinyl alcohol, and 1.6hexamethylenediamine in the structure under the influence of biological medium 199 for 1, 3 and 6 months were conducted. IR spectroscopy and physical-mechanical tests of these film materials before and after incubation in biological medium 199 were investigated. According to research results, there are decrease of the tensile strength (in 1.29-2.50 times) and a relative elongation at break (in 1.15-1.91 times) after incubation in biological medium 199. It is established that under the influence of biological medium 199 there are processes of biodegradation of film materials. The introduction of D-cycloserine into the composition of polyurethaneurea contributes to their biodegradation. It allows us to conclude that biodegradation is due to release of D-cycloserine. The study of the dynamics of D-cycloserine release from the polymer matrix was conducted by spectrophotometric method. The amount of drug varies depending on the copolymer content in structure of film materials (75.00-96.71% of the total amount of the introduced drug). It has been established that the studied film materials are capable to the prolonged release of D-cycloserine. It allows using them as film coatings for medicine with different ability to release of drug depending on requirements.

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Antibiotic Effects on Methicillin-Resistant Staphylococcus aureus Cytoplasmic Peptidoglycan Intermediate Levels and Evidence for Potential Metabolite Level Regulatory Loops

Cited by 18 publications

References 43 publications

Susceptibility of Ocular Staphylococcus aureus to Antibiotics and Multipurpose Disinfecting Solutions

Susceptibility of Ocular Staphylococcus aureus to Antibiotics and Multipurpose Disinfecting Solutions

Mechanism of BceAB-type transporter: Resistance by lipid II flipping

Study of Biodegradation of Film Materials with D-Cycloserine Based on Polyurethaneurea and the Dynamics of Drug Release

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