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  • One significant finding in this study was the overexpression

    2019-10-08

    One significant finding in this study was the overexpression of a protein identified as LysM domain/BON superfamily protein [29], [30]. This protein was highly overexpressed in the meropenem-treated condition. InterProScan analysis revealed that the LysM domain/BON superfamily protein consisted of two domains, the lysine M domain and the BON domain. The gene encoding this protein (ygaU) has been found to be under the direct regulation of σS (or RpoS), a subunit of RNA polymerase that is a master regulator of the general stress response. In E. coli, σS was shown to be strongly induced upon entry into many stress conditions and/or stationary phase and was important for the expression of several stress resistances [31], [32]. In 2014, a study conducted by Bernal-Cabas et al. suggested a possible role for LysM domain/BON superfamily protein in peptidoglycan (PG) structure modification mediated by the Cpx envelope stress response, resulting in complex pilocarpine hydrochloride to envelope stress in E. coli. The Cpx pathway directly regulates several genes for periplasmic protein folding and cell wall remodelling, including ygaU. The Cpx envelope stress response participates in PG homeostasis by sensing cell wall perturbations and escalates a response by stimulating these genes to alleviate it. The study indicated that LysM domain/BON superfamily protein, along with another protein called l,d-transpeptidase, modified the PG cross-linking pattern [33]. More recently, a study carried out in E. coli showed activation of the Cpx envelope stress response when cells were exposed to antibiotics such as β-lactams, specifically inhibiting cell wall division or elongation machinery [34]. In the current study, overexpression of LysM domain/BON superfamily protein under meropenem stress suggests that it might be involved in the resistance mechanism in K. pneumoniae. It is quite possible that the same Cpx pathway is initiated, as a result of which ygaU becomes stimulated; this protein then modifies PG cross-linking making bacterial cell walls less susceptible to meropenem. The drug itself might be acting as a stimulator triggering the action of YgaU to engage in PG remodelling. The present data suggest that YgaU might play an important role in developing resistance in bacteria, but this aspect needs more elaborative research.
    Conclusion
    Funding The Department of Biotechnology is highly acknowledged for the DBT Award BT/HRD/NBA/34/01/2012 and grant BT/PR8281/BID/7/448/2013 to AUK. The Promotion of University Research and Scientific Excellence (DST-PURSE) Program Phase-II No. SR/PURSE Phase 2/9 is highly acknowledged for infrastructure support.
    Competing interests
    Ethical approval
    Introduction Clostridium difficile is a major causative agent of hospital-acquired diarrhoea. Molecular typing of clinically significant C. difficile isolates is a crucial tool for surveillance and spread control of C. difficile infections (CDI). The typing approaches are focused on conserved parts, repetitive regions or entire genomes (Knetsch et al., 2013). They include PCR-ribotyping (Bidet et al., 1999, Stubbs et al., 1999, Indra et al., 2008, Fawley et al., 2015), multi-locus sequence typing (MLST) (Griffiths et al., 2010), toxinotyping (Rupnik, 2010), multi-locus variable tandem-repeats analysis (MLVA) (van den Berg et al., 2007) and whole-genome sequencing (Eyre et al., 2013). The Czech Republic participated in the European Clostridium difficile infection surveillance Network (ECDIS-net), a European Centre for Disease Prevention and Control (ECDC) supported project that started in 2011 and focused on building laboratory capacity for pan-European Clostridium difficile infection (CDI) surveillance. In relation to this project, the department of Medical Microbiology of Motol University Hospital introduced CE-ribotyping, and 2201 Czech C. difficile isolates were sent from 32 hospitals for molecular typing over a three-year period (2013–2015).