CrrAB-dependent capsule formation in K.pneumoniae

Abstract

The pace at which multidrug-resistant bacteria (MDR) are increasing and spreading around the world is worrying and it is now recognised by the World Health Organization as a public health threat (Shrivastava, Shrivastava and Ramasamy, 2018). To give a scale on the pressing issue, Jim O’ Neill in his report on anti-microbial resistance (AMR) predicted a drastic increase in deaths caused by MDR bacteria, potentially reaching 50.000.000 deaths per year by 2050 (Review on Antimicrobial Resistance, 2016). Bacteria can acquire resistance through transmission of antimicrobial resistance genes (carried either on bacterial chromosome, plasmids, or transposons), to multiple antibiotics. Thus, creating MDR bacteria (Paterson, 2004).

In order to raise awareness, the World Health Organization (WHO) has recently identified the ESKAPES (E. faecium, S. aureus, K.pneumoniae, A. baumannii, P.aeruginosa, Enterobacter spp. , S. maltophila) group of pathogens which pose an imminent threat to human and animal health as antibiotic options against these bacteria are limited (Antibiotic-resistant priority pathogens list, 2017).

To be precise, carbapenem resistant A. baumannii and P. aeruginosa, extended spectrum β-lactamase (ESBL) or carbapenem resistant K. pneumoniae and Enterobacter spp. are listed in the critical priority list of pathogens. Vancomycin resistant E. faecium (VRE) and methicillin and vancomycin resistant S. aureus (MRSA and VRSA) are in the high priority group (Antibiotic-resistant priority pathogens list, 2017). Klebsiella pneumoniae in the clinical setting.

The critical priority list consists of three pathogens which amount for most nosocomial infections. Klebsiella pneumoniae and Acinetobacter spp. interchange between the highest rate of infection (Agaba, Tumukunde, Tindimwebwa and Kwizera, 2017). The high infection rate is attributed to their ability to exhibiting multiple pathogenesis routes leading to a plethora of symptoms. These can range from pneumoniae to liver abscesses and septic shock, ultimately proving lethal if left untreated. Furthermore, their virulence can greatly increase through the acquisition of mobile elements (such as pathogenicity islands) or through chromosomal mutations leading to increased avoidance of the host immune system (Podschun and Ullmann, 1998). Overall, these capabilities make them successful in colonization of the host and in producing disease. But they do not render treatment regimens ineffective. Thus, the major threat lies when these capabilities are coupled to extensive resistance to antibiotics. One of the most studied examples is the increased mortality rate associated with MDR K.pneumoniae arising from the recent surge in AMR.