Abstract
Bacteria evolving resistance against the action of multiple drugs and its ability to disseminate the multidrug resistance trait(s) across various strains of the same bacteria or different bacterial species impose serious threat to public health. Evolution of such multidrug resistance is due to the fact that, most of the antibiotics target bacterial survival mechanisms which exert selective pressure on the bacteria and aids them to escape from the action of antibiotics. Nonetheless, targeting bacterial virulence strategies such as bacterial surface associated polysaccharides biosynthesis and their surface accumulation mechanisms may be an attractive strategy, as they impose less selective pressure on the bacteria. Capsular polysaccharide (CPS) or K-antigen that is located on the bacterial surface armors bacteria from host immune response. Thus, unencapsulating bacteria would be a good strategy for drug design, besides CPS itself being a good vaccine target, by interfering with CPS biosynthesis and surface assembly pathway. Gram-negative Escherichia coli uses Wzy-polymerase dependent (Groups 1 and 4) and ATP dependent (Groups 1 and 3) pathways for CPS production. Considering E. coli as a case in point, this review explains the structure and functional roles of proteins involved in Group 1 Wzy dependent CPS biosynthesis, surface expression and anchorage in relevance to drug and vaccine developments.
Highlights
Discovery of antibiotics revolutionized modern medicine by protecting millions of people from life-threatening bacterial infections (Ventola, 2015)
WHO’s (2014) report on Assembly Machinery resistance (AMR) states that extensively drug-resistant tuberculosis (XDR-TB) has increased to 9.2% among the reported multidrug resistance (MDR)-TB cases, wherein, drugs like rifampicin, ethambutol, pyrazinamide and isoniazid have become ineffective against the pathogen Mycobacterium tuberculosis
Bacteria acquire resistance to antibiotics through chromosomal gene mutations known as vertical evolution that can subsequently be transmitted to other bacterial strains through horizontal gene transfer (HGT) (Poole, 2011; Radhouani et al, 2014; von Wintersdorff et al, 2016)
Summary
Discovery of antibiotics revolutionized modern medicine by protecting millions of people from life-threatening bacterial infections (Ventola, 2015). Though antibiotics underpin important medical advancements in the 20th century, development of resistance against their action to combat bacterial infections is increasingly common in recent years and emerged as one of the greatest threats to human health (Davies and Davies, 2010). WHO’s (2014) report on AMR states that extensively drug-resistant tuberculosis (XDR-TB) has increased to 9.2% among the reported MDR-TB cases, wherein, drugs like rifampicin, ethambutol, pyrazinamide and isoniazid have become ineffective against the pathogen Mycobacterium tuberculosis. MDR is increasingly common in recent years and expensive to treat. A recent report prepared by economist O’Neill (2016) warns that a failure to tackle AMR would claim 10 million lives each year by 2050
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