Insertion element mediated <em>mgr</em>B disruption and presence of ISKpn28 in colistin-resistant <em>Klebsiella pneumoniae</em> isolates from Saudi Arabia

Abstract

BackgroundIn Klebsiella pneumoniae, mgrB and components of pmrHFIJKLM operon play a major role in colistin resistance.MethodsWe analyzed 23 nonduplicating colistin-resistant K. pneumoniae isolates, collected during the years 2011–2015, for the possible mechanism underlying their nonsusceptibility to colistin. Isolates were tested for their minimum inhibitory concentrations and antibiotic resistance determinants and genotyped by multilocus sequence typing (MLST). The MLST genes, antibiotic-resistant genes, and the genes of two component system (TCS), including mgrB, PhoQ/PhoP, pmrA/B, and CrrAB, were investigated by PCR amplification and Sanger sequencing.ResultsAll isolates were distributed in eight sequence types (STs) and showed mutations either in mgrB or PhoP genes. ISKpn14 was found in 10, ISKpn28 in four, and IS903 in three isolates. One isolate showed deletion of a single nucleotide in mgrB open reading frame causing premature stop codon. L26Q substitution in PhoP was found in five isolates.ConclusionThe mutations in mgrB were mostly mediated by insertion elements (IS). ISKpn14 is the major IS while ISKpn28 is reported for the first time in mediating mgrB disruption. IS903, an IS5 family member, involved in mgrB disruption in three ST-152 NDM-1-positive isolates, was previously responsible for omp-36 disruption in our carbapenem-resistant K. pneumoniae and appears to contribute to transform the isolates into a pan-drug ones. Also, the abundance of insertion sites in mgrB indicates the plasticity of this gene. In our isolates, IS-mediated colistin resistance appears to be a later phenomenon than mutation in PhoP gene.

High contribution and impact of resistant gram negative pathogens causing surgical site infections at a multi-hospital healthcare system in Saudi Arabia, 2007–2016

“…On the other hand, the current rates were even lower than the extremely high rates of cephalosporin and carbapenem resistance among GNPs reported in some developing countries such as Egypt [13], India [29], and Iran [14]. The high rate of resistance in GNPs in the current study is probably reflecting a wide range of resistance mechanisms in GNPs observed in our hospitals, such as NDM, OXA 48 and MGrb and outer membrabe protein (OMP) resistance [30][31][32][33][34]. The high rate of resistance in GNPs in the current study is quite alarming as it already increased the mortality by 25%.…”

<p>Rapid Emergence of a Pandrug-Resistant <em>Klebsiella pneumoniae</em> ST11 Isolate in an Inpatient in a Teaching Hospital in China After Treatment with Multiple Broad-Spectrum Antibiotics</p>

“…The insertion interrupts the coding sequence of mgrB and may contribute to the colistin resistance of KP65. 20 Moreover, a single-base substitution, G169C, leading to the amino acid substitution V57L, was detected in the rpsJ gene. This mutation may contribute to tigecycline resistance in this isolate.…”

Colistin Use and Its Resistance in Kingdom of Saudi Arabia: A Narrative Review

“…For instance, colistin-resistant Enterobacteriaceae spp. and Acinetobacter spp., in particular A. baumannii, have been identified [16] [17], and infections caused by specific strains of Klebsiellapneumoniae with remarkable resistances to colistin have been recently specified [18]. Pathogenic Gram-negative bacteria with well-known intrinsic resistant to colistin such as Proteus, Serratia, and Morganella have widely isolated [16].…”

“…In support, mcr-1 gene-mediated bacterial resistance to colistin has been characterized in several worldwide countries [20], and it was detected not only in infected human samples, but also in foods, animals, and environments [21] [22], reflecting its increased horizontal transfer around the world [23]. In addition to the prevalence of mcr-1 gene, emergence of Klebsiella pneumoniae harboring mutated mgrB-colistin-resistance gene has also been recently raised in Saudi Arabia [18]. Mutations or inactivation in this bacterial gene have previously been identified as the key step in development of bacterial CrrAB and PhoQ/PhoP signaling system mediating colistin resistance [24].…”

“…In the hospitals and clinical centers, systemic therapy with colistin preparations is generally carried out by intravenous injection. Colistin can also be injected intramuscularly, however, it is not recommended route due to its very painful effect [18]. Most importantly, there is still non optimized systemic dosing strategy regarding the appropriate colistin usage throughout the world [11] [25] [26] and dose-related nephro-and neurotoxicity is an important adverse effect in colistin therapy [27].…”