Diversity and Genetic Basis for Carbapenem Resistance in a Coastal Marine Environment

Abstract

Resistance to the “last-resort” antibiotics, such as carbapenems, has led to very few antibiotics being left to treat infections by multidrug-resistant bacteria. Spread of carbapenem resistance (CR) has been well characterized for the clinical environment. However, there is a lack of information about its environmental distribution. Our study reveals that CR is present in a wide range of Gram-negative bacteria in the coastal seawater environment, including four phyla, eight classes, and 30 genera. These bacteria were likely introduced into seawater via stormwater flows. Some CR isolates found here, such as Acinetobacter junii, Acinetobacter johnsonii, Brevundimonas vesicularis, Enterococcus durans, Pseudomonas monteilii, Pseudomonas fulva, and Stenotrophomonas maltophilia, are further relevant to human health. We also describe a novel metallo-β-lactamase (MBL) for marine Rheinheimera isolates with CR, which has likely been horizontally transferred to Citrobacter freundii or Enterobacter cloacae. In contrast, another MBL of the New Delhi type was likely acquired by environmental Variovorax isolates from Escherichia coli, Klebsiella pneumoniae, or Acinetobacter baumannii utilizing a plasmid. Our findings add to the growing body of evidence that the aquatic environment is both a reservoir and a vector for novel CR genes. IMPORTANCE Resistance against the “last-resort” antibiotics of the carbapenem family is often based on the production of carbapenemases, and this has been frequently observed in clinical samples. However, the dissemination of carbapenem resistance (CR) in the environment has been less well explored. Our study shows that CR is commonly found in a range of bacterial taxa in the coastal aquatic environment and can involve the exchange of novel metallo-β-lactamases from typical environmental bacteria to potential human pathogens or vice versa. The outcomes of this study contribute to a better understanding of how aquatic and marine bacteria can act as reservoirs and vectors for CR outside the clinical setting.

Carbapenem Resistance among Marine Bacteria—An Emerging Threat to the Global Health Sector

“…The dissemination of AR in seawater may be influenced by discharges from coastal runoff, aquaculture, polluted rivers, and WWTP effluents, which frequently contain resistant bacteria and resistant genes [72][73][74][75][76][77]. A study described that CRB communities in seawater and storm water samples did not differ significantly at the investigated sites, and the phylogenetic analysis showed that their CR isolates often belonged to the same species [25]. CPE, such as Enterobacter spp.…”

“…Thus, local sources, such as stormwaters and rivers, are an important source of CRB in the seawater and may have a significant effect on the composition of CRB in the marine environment (see Figure 1). Furthermore, CR has also been recently detected in the marine environment [25,73,76,[78][79][80]. For example, CRB belonging to a wide range of bacterial taxa, including four phyla, eight classes, and 30 genera, were found in Australian marine and near-shore environments [25].…”

“…Furthermore, CR has also been recently detected in the marine environment [25,73,76,[78][79][80]. For example, CRB belonging to a wide range of bacterial taxa, including four phyla, eight classes, and 30 genera, were found in Australian marine and near-shore environments [25]. Many genera found in the marine environment, such as Pseudomonas [9,81], Stenotrophomonas [81], Acinetobacter [51,82,83], Brevundimonas [84], Caulobacter [85], Chryseobacterium [86,87], Empedobacter [88], Sphingomonas [86], Flavobacterium [89], Cupriavidus [81], Myroides [89], Ochrobactrum [90], and Pedobacter [86], have already been previously described to contain CR, and these bacteria may carry well-known and clinically relevant CRGs.…”

“…Furthermore, E. coli from terrestrial sources could transfer its bla CTX-M-15 gene to Pantoea agglomerans and Raoultella terrigena in the coastal seawater [108]. Another study reported that in seawater samples, Rheinheimera spp., which are typical marine bacteria [109,110], have been found to share an identical MBL gene utilizing plasmid transfer and chromosomal integration with the species C. freundii and E. cloacae, which are not typically found in seawater [25]. In addition, Variovorax spp.…”

“…Alarmingly, carbapenem resistance (CR) has been reported globally [15][16][17], with the synthesis of carbapenemases being the most common mechanism underpinning resistance [15,[17][18][19]. Furthermore, several cases of CR have been reported in bacteria outside the hospital setting, including rivers [20], sewage [21,22], and marine waters [23][24][25][26]. This review summarizes the knowledge on the spread of CR outside of the clinical setting with particular focus on the potential of the marine environment to act as a reservoir for the genetic transfer of CR among bacteria.…”