Whole Genome Sequencing of a Citrobacter freundii Strain Isolated from the Hospital Environment: An Extremely Multiresistant NDM-1 and VIM-48 Coproducing Isolate

Abstract

Citrobacter freundii has acquired resistance to several antimicrobial drugs, including last-resort antibiotics affecting, therefore, clinical efficacy and causing high rates of mortality. In this study, we investigate the whole genome sequence of a carbapenem-resistant C. freundii strain isolated from the hospital environment in Tunisia. A total of 210 samples were taken using sterile swabs, from inanimate surfaces, medical devices, and care staff, during the period extended between March and April 2019. After the microbiological analysis of samples and antimicrobial susceptibility testing, only one strain identified as C. freundii showing resistance to carbapenems was selected for the whole genome sequencing. The genome analysis revealed a high-level resistance to most antibiotics. Interestingly, we have noted the coexistence of bla NDM-1 and bla VIM-48 metallo-b-lactamase (MBL) encoding genes conferring resistance to carbapenems. Other b-lactamases encoding genes have also been detected, including bla TEM-1 , bla CMY-48 , and bla OXA-1 . Moreover, genes conferring resistance to aminoglycoside [aac(3)-IId, ant(3 †)-Ia, aadA, aac(6¢)-Ib], macrolide [mph(A)], sulfonamide (sul1), trimethoprim (dfrA1), tetracycline [tet(D)], chloramphenicol [cat(B3)], rifamycin (arr-3), and quinolone (qnrB) have been revealed. The multi-locus sequence typing analysis showed that this isolate could not be assigned to an existing sequence type (ST), but it is almost identical to ST22. The plasmid investigation revealed the presence of five plasmids belonging to diverse incompatibility groups (IncFII, IncHI1A, IncHI1B, IncN, and IncX3). To the best of our knowledge, our findings report the first detection of NDM-1 and VIM-48 coproducing C. freundii in Tunisia and the second detection in the world of the bla VIM-48 .

Molecular Epidemiology of Global Carbapenemase-Producing Citrobacter spp. (2015–2017)

“…population is dominated by diverse STs with different characteristics and varied geographical distributions. ST22 and ST98 isolates with different carbapenemases (VIMs, KPC-2, NDM-1, OXA-48) were previously reported from Spain ( 21 , 22 ), Tunisia ( 23 ) and Germany ( 24 ).…”

Global prevalence, characteristics, and future prospects of IncX3 plasmids: A review

“…Isolates harboring IncX3 plasmids are found in many countries around the world ( Figure 1 ), including China (CHN), South Korea (KOR), Switzerland (SWI), Czech (CZE), Italy (ITA), Australia (AUS), India (IND), Japan (JPN), Netherlands (NED), Brazil (BRA), Germany (GER), South Africa (ZAF), Myanmar (MYA), the United States (USA), France (FRA), Ghana (GHA), Spain (ESP), the United Arab Emirates (AE), Cambodia (CAM), Canada (CAN), Denmark (DEN), Egypt (EGY), Kuwait (KUW), Pakistan (PAK), Poland (POL), Portugal (POR), the United Kingdom (UK), Oman (OMA), Vietnam (VIE), Algeria (DZA), Angola (AGO), Burkina Faso (BFA), Chad (TCD), Nigeria (NGA), Tanzania (TZA; Supplementary material ), Tunisia (TUN; Dziri et al, 2022 ), Lebanon (LBN; Dagher et al, 2018 ), Ethiopia (ETH; Legese et al, 2022 ), Croatia (HRV; Petrosillo et al, 2016 ), Turkey (TUR; Peirano et al, 2022 ), and Gabon (GAB; Moussounda et al, 2017 ). Among them, China is the country with the most reported IncX3 plasmids.…”

A brief insight into Citrobacter species - a growing threat to public health

“…Bacteremia caused by Citrobacter spp. can be nosocomial or community-acquired (Doran, 1999;Lai et al, 2010;Dziri et al, 2022). Also, infections caused by Citrobacter spp.…”

“…Studies on carbapenemresistant Citrobacter spp. found that the Inc family of plasmids was the primary group that carries genes for carbapenem resistance (Cao et al, 2021;Dziri et al, 2022;Ju et al, 2022); and was one of the main reasons for the rapid dissemination of carbapenem-resistant Citrobacter spp. around the world.…”