Role of Bacteria in Urinary Tract Infections
K. Balamurugan, U. Prithika in Pocket Guide to Bacterial Infections, 2019
In 1959, Methicillin was introduced to treat penicillin-resistant S. aureus–related diseases. Methicillin-resistant S. aureus (MRSA) was emerged in the UK around 1961 and spread around European countries and then to Japan, Australia, and the United States. The methicillin-resistance gene (mecA) encodes a methicillin-resistant penicillin-binding protein that is not present in susceptible strains and is believed to have been acquired from a distantly related species. mecA is carried on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec), of which four forms have been described that differ in size and genetic composition. Many MRSA isolates are multiresistant and are susceptible only to glycopeptide antibiotics such as vancomycin and investigational drugs. MRSA isolates that have decreased susceptibility to glycopeptides (glycopeptide intermediately susceptible S. aureus [GISA]), reported in recent years, are a cause of great public health concern (Martin et al., 2002). Community-related MRSA is associated with increased disease severity, ranging from cutaneous abscesses to deadly necrotizing pneumonia. USA300 and USA400 are the two dominant CA- MRSA strains. The USA400 strain causes deadly infections but in less frequency, whereas USA300 was widespread and mainly related with community infections and life-threatening infections like necrotizing pneumonia (Wu et al., 2010).
Green Metal-Based Nanoparticles Synthesized Using Medicinal Plants and Plant Phytochemicals against Multidrug-Resistant Staphylococcus aureus
Richard L. K. Glover, Daniel Nyanganyura, Rofhiwa Bridget Mulaudzi, Maluta Steven Mufamadi in Green Synthesis in Nanomedicine and Human Health, 2021
MRSA resistance is rooted in the production of a novel low-affinity penicillin-binding protein (PBP2a or PBP2’), which reduces the binding affinities of β-lactam antibiotics (Hartman and Tomasz, 1984; Reynolds and Brown, 1985; Utsui and Yokota, 1985). The mecA gene has been reported responsible for encoding the PBP2a (Jevons, 1961; Katayama et al., 2000). MRSA can continue with cell wall synthesis regardless of the presence of high concentrations of β-lactam antibiotics (Matthews and Tomasz, 1990). The mecA gene that encodes PBP2a is located on MRSA chromosome. The sequence of mecA gene was determined in Japan in 1987, when it was cloned from a MRSA strain (Staphylococcus aureus, TK784) (Song et al., 1987). The mecA gene was found to be distributed among coagulase-negative Staphylococcus strains as well as S. aureus (Hürlimann-Dalel et al., 1992; Suzuki et al., 1992). Therefore, the methicillin resistance determinant (mec) was hypothesized as to being able to transfer freely among Staphylococcal species. This mecA might have entered S. aureus only once or twice (Barry et al., 1993).
Ceftobiprole
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Banerjee et al. (2008) selected for ceftobiprole-resistant MRSA mutants by serial passage of broth cultures in subinhibitory concentrations of ceftobiprole for 1 month. Three strains developed high-level homogeneous resistance to ceftobiprole within 3 weeks (MICs 128–256 μg/ml). A strain with plasmid-encoded wild-type mecA developed five new mutations in mecA, resulting in amino acid changes near penicillin-binding motifs. A strain with plasmid-encoded mutant mecA with four baseline PBP2a mutations developed four new mutations in mecA in response to ceftobiprole exposure. In both of these two strains, loss of mecA converted highly resistant strains into fully susceptible ones. A third strain, COLnex pAW8, was mecA negative at baseline. High-level ceftobiprole resistance developed in this strain in response to exposure to ceftobiprole, presumably due to a non-mecA mechanism related to chromosomally encoded genes (Banerjee et al., 2008).
The application of machine learning techniques to innovative antibacterial discovery and development
Published in Expert Opinion on Drug Discovery, 2020
Mateus Sá Magalhães Serafim, Thales Kronenberger, Patrícia Rufino Oliveira, Antti Poso, Káthia Maria Honório, Bruno Eduardo Fernandes Mota, Vinícius Gonçalves Maltarollo
Lastly, changes in drug targets can also be relevant in Gram-positive bacteria. Two decades after the discovery of penicillinase-producing Staphylococcus aureus in the 1940’s, the methicillin-resistant S. aureus (MRSA) was discovered. This resistance is mainly mediated by the product of the mecA gene, which encodes a variant of the penicillin binding protein (PBP). This variant (PBP2A) has a lower affinity for penicillin, allowing the peptidoglycan synthesis to occur even in the presence of these antibiotics [28]. Also relevant is the vancomycin-resistance mechanism in Enterococcus spp. and S. aureus (vancomycin-resistant Enterococcus – VRE and vancomycin-resistant S. aureus – VRSA), in which the modification of D-Ala-D-Ala residues to D-Ala-D-Lac in the lateral peptide chains prevents the binding of drugs and the inhibition of the cell wall synthesis [29,30]. This mechanism of resistance can be observed in Gram-negative, such extended-spectrum cephalosporins resistant Neisseria gonorrhoeae [26].
Recovery of borderline oxacillin-resistant Staphylococcus pseudintermedius (BORSP) from bone and soft tissue of a rheumatoid arthritis patient with severe osteoporosis: transmission from the family dog
Published in Journal of Chemotherapy, 2021
Leah D. Blondeau, Stephen Sanche, David J. Sauder, Harry Deneer, Rani Kanthan, Joseph E. Rubin, Beverly J. Morrison, Joseph M. Blondeau
S. pseudintermedius was isolated from this patient on 3 separate occasions (4 specimens) over a 9 month period (Table 1). Susceptibility profiles for the S. pseudintermedius strains (human and dog) are summarized in Table 2. For the strain from specimens collected on 24 September 2018, the organism was pan-susceptible to the drugs tested. A similar organism (same antibiogram profile) was not recovered from the patient’s dog. For the strains recovered on 12 May 2019 and 18 June 2019, the antimicrobial profiles were the same and had the same antimicrobial profile as the strains recovered from the patient’s dog on 8 November 2019. These strains showed a more resistant phenotype including resistance to oxacillin, ampicillin, clindamycin and erythromycin. The strains from 18 June 2019 and the family dog were susceptible to amoxicillin-clavulanic acid. Testing by polymerase chain reaction (PCR) for the mecA gene was negative as was latex agglutination for penicillin binding protein 2a. Testing of the strain from 18 June 2019 and from the dog by cefinase disc (Becton Dickinson, Toronto, Canada) showed both strains to be positive for β-lactamase enzyme.
Evaluation of fosfomycin combined with vancomycin against vancomycin-resistant coagulase negative staphylococci
Published in Journal of Chemotherapy, 2020
Yasser Musa Ibrahim, Wael Mohamed Abu El-Wafa
We selected 8 CoNS isolates showing the highest levels of resistance to both oxacillin and vancomycin for further phenotypic and genotypic characterization of oxacillin and glycopeptide (vancomycin and teichoplanin) resistance. The oxacillin-sensitive, vancomycin-intermediate S. saprophyticus (isolate CoNS-15) and S. aureus ATCC 29737, which is sensitive to both oxacillin and vancomycin, were included for quality control purposes. Phenotypically, data revealed that all vancomycin-resistant isolates (MIC 32 mg/L) showed very high oxacillin MIC values; with oxacillin MIC reaching 512 mg/L in case of S. caseolyticus (CoNS-51) isolate (Table 4). Moreover, 3 isolates were resistant to both glycopeptides, with teichoplanin MIC range of 16->32 mg/L. The other 5 isolates were teichoplanin-sensitive. On the molecular level, mecA gene was detected in all oxacillin-resistant isolates. In contrast, vanA gene was detected in only one (S. hominis CoNS-8) and vanB in two (S. epidermidis CoNS-46 and S. caseolyticus CoNS-51) of the studied isolates (Table 4).
Related Knowledge Centers
- Antibiotic
- Bacteria
- Cell Wall
- Methicillin
- Beta-Lactam Antibiotics
- Methicillin-Resistant Staphylococcus Aureus
- Staphylococcus
- Sccmec
- Hospital-Acquired Infection
- Penicillin-Binding Proteins