Novel Pseudomonas aeruginosa Strains Co-Harbouring blaNDM-1 Metallo β-Lactamase and mcr-1 Isolated from Immunocompromised Paediatric Patients

Abstract

Background The rising resistance to carbapenems in Gram-negative bacteria worldwide poses a major clinical and public health risk. This study aimed to characterise carbapenem- and colistin-resistance genes, bla NDM-1 and mcr-1 located on IncX4 plasmid in MDR Pseudomonas aeruginosa , isolated from paediatric patients undergoing chemotherapy as a result of leukaemia. Methods In this study, six carbapenem-resistant strains of P. aeruginosa were isolated from two paediatric patients under chemotherapy treatment (1.8 years old female and 2.1 years male) from the Shenzhen Hospital, China, in the year 2019. Isolates were screened for conventional antibiotics such as tobramycin, cefepime, imipenem, and ciprofloxacin in additional colistin by using the broth dilution method. Furthermore, resistance determinants: mcr-1, bla NDM-1, bla KPC-1, and bla GES were screened using PCR and sequencing followed by multi-locus sequence typing. The horizontal gene transfer and location of mcr-1 and bla NDM-1 were determined by a liquid mating assay. In addition, Incompatibility type (Inc), PCR-based replicon type, and subgroup (MOB) of plasmid were studied. Results The screening for conventional antibiotics isolates showed 100% resistance to all the tested antibiotics except tobramycin. All isolates harboured carbapenemase encoding bla NDM-1 , of which three also had mcr-1 located on a single IncX4 transferable plasmid. MLST typing revealed that four strains had a novel (new) STs type, while two belonged to ST1966. Conclusion This study identified for the first time colistin- and carbapenem-resistant MDR P. aeruginosa in paediatric patients with leukaemia in Shenzhen, China. It highlights the need for continuous surveillance in high-risk clones of MDR P. aeruginosa . Prudent use of antibiotics based on local antimicrobial susceptibility and clinical characteristics can help in reducing mortality in immunocompromised patients.

Genomic epidemiology and mechanisms of antibiotic resistance in Pseudomonas aeruginosa isolated from children’s hospital in Shenzhen, China

“…ST1963 was rst reported in Kunming, China with bla KPC-2 carbapenemase and this region is close to Shenzhen, possibly indicating the spread of this clone in the surrounding area. All our ST381 and ST234 isolates were carbapenem-resistant and this has been observed in a previous study [39]. In a different study, it was observed that P. aeruginosa strain BH9 belonging to ST381 was positive for the bla KPC-2 carbapenemase present on a phage-like plasmid on the contrary our ST381 isolates possessed either bla NDM-1 (n = 6) or bla NDM-55 (n = 7) carbapenemase instead [40].…”

Detection of Plasmid-Mediated Resistance against Colistin in Multi-Drug-Resistant Gram-Negative Bacilli Isolated from a Tertiary Hospital

“…In this study, mcr genes were not found in P. aeruginosa . However, as colistin is the last-resort antibiotic against strains of this organism resistant to carbapenems, reports of mcr genes among multi-drug-resistant strains of this species have started to emerge [ 32 , 33 ], and the horizontal transmission of mcr -1 genes has been shown to occur from P. aeruginosa to other bacterial species [ 34 ], the surveillance of mcr -carrying P. aeruginosa strains remains highly encouraged.…”

Boosting succinylation-dependent LPS biosynthesis to overcome colistin resistance

“…Alarmingly, mcr-1 coexpressed with extended-spectrum beta-lactamase and carbapenemase resistance genes are also detected 10,11 , presenting a severe challenges to human health.…”

“…Not surprisingly, polymyxin-resistant bacterial strains are frequently detected in environmental and hospital isolates worldwide 7 . The emergence of mobilized colistin-resistant gene (mcr-1) that confer resistance to polymyxins alerts human society of the misuse of polymyxins so that they are banned in animal husbandry and aquaculture in many countries 8,9 .Alarmingly, mcr-1 coexpressed with extended-spectrum beta-lactamase and carbapenemase resistance genes are also detected 10,11 , presenting a severe challenges to human health.Colistin, the most common type of polymyxins, disrupts bacterial membrane integrity through electrostatic interaction between positively charged colistin and negatively charged lipid A moieties of lipopolysaccharide (LPS), and cationic displacement (Ca 2+ and Mg 2+ ) of LPS, which cause the leakage of intracellular contents and ultimately trigger cell lysis 12,13 . Accordingly, bacteria adjusting LPS charge to reduce electrostatic interaction has been considered as one of the most important strategies to evade colistin killing 14 .…”