Proteomics and Docking Study Targeting Penicillin-Binding Protein and Penicillin-Binding Protein2a of Methicillin-Resistant Staphylococcus aureus Strain SO-1977 Isolated from Sudan

Abstract

Whole genome sequencing of methicillin-resistant Staphylococcus aureus (MRSA) strain isolated from Sudan has led to a great deal of information, which allows the identification and characterization of some pivotal proteins. The objective of this study was to investigate the penicillin-binding proteins, PBP and PBP2a, of SO-1977 strain to have insights about their physicochemical properties and to assess and describe the interaction of some phytochemicals against them in silico. PBP and PBP2a from MRSA’s Sudan strain were found to be of great resemblance with some other strains. G246E single-nucleotide polymorphism was reported and identified in the allosteric binding site positioned in the non-penicillin-binding domain. The docked compounds demonstrated good binding energies and hydrogen bond interactions with residue Ser404 which plays crucial roles in β-lactam activity. This finding would contribute significantly to designing effective β-lactam drugs, to combat and treat β-lactam–resistant bacteria in the future.

The Effect of Rotating Magnetic Field on Susceptibility Profile of Methicillin-Resistant Staphylococcus aureus Strains Exposed to Activity of Different Groups of Antibiotics

“…Furthermore, to determine whether the observed changes in antibiotic susceptibility due to the RMF exposure were strain-specific, not only the reference strains, but also seven clinical MRSA isolates were included in the study. It is well established that methicillin resistance level is not identical between staphylococcal strains [ 38 ]. For example, methicillin resistance is mediated by the expression of an altered PBP2 protein (called PBP2a) characterized by a low affinity for β-lactam antibiotics, resulting in resistance to most β-lactams [ 34 ].…”

“…For example, methicillin resistance is mediated by the expression of an altered PBP2 protein (called PBP2a) characterized by a low affinity for β-lactam antibiotics, resulting in resistance to most β-lactams [ 34 ]. However, PBP2a encoded by the mecA gene, which is carried on a mobile genetic element known as a staphylococcal cassette chromosome mec (SCC mec ), can be regulated by two independent regulatory systems ( mecI – mecR – mecR2 and blaI – blaR ) and multiple chromosomal genes [ 38 ]. Additionally, because MRSA strains, in addition to resistance to β-lactam antibiotics, can also be resistant to a number of antibiotics belonging to other classes [ 7 ], for comparison purposes, one methicillin-sensitive (lacking the mecA gene and showing susceptibility to methicillin in a phenotypic test with a cefoxitin-saturated disc) reference strain was used in the study.…”

“…Summarizing the previous stages of the analyses, the most promising results related to the possibility of using RMF to change the antibiotic resistance of MRSA strains concern two groups of antibiotics, β-lactams and glycopeptides, the common feature of which is the site of their antimicrobial activity, i.e., the bacterial cell wall. We are aware that, although the general mechanism of action of β-lactam antibiotics is similar, there are some differences in their specific activity, e.g., related to different binding sites with the PBP2a protein or to the binding energy value [ 38 , 42 ]. Similarly, in a group of glycopeptide antibiotics, the relationship between vancomycin and teicoplanin minimum inhibitory concentration (MIC) is not clearly defined [ 48 , 49 ].…”

Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets?

“…Likewise, STPKs play a role during growth and β-lactam susceptibility of Corynebacterium spp. [68,69], B. subtilis [70][71][72][73][74], M. tuberculosis [60,[75][76][77][78][79][80], and other species. Therefore it is not unexpected that several kinase inhibitors of diverse structural classes used in human medicine increased susceptibilities of various bacterial species to cell wall active antibacterial agents.…”

Bioinformatics in Sudan: Status and challenges case study: The National University-Sudan

“…An example is the whole genome sequencing of gram-negative bacteria and gram-positive bacteria isolated from Sudanese patients including Escherichia coli [ 20 ], Pseudomonas aeruginosa [ 21 ], and Methicillin-Resistant Staphylococcus aureus (MRSA) [ 22 ]. Furthermore, a proteomics and molecular docking study performed on MRSA strains can provide insights into combating β-lactam–resistant bacteria in the future [ 23 ].…”