Carbapenem resistance in environmental bacteria

The widespread emergence and resistance of carbapenem-resistant bacteria (CRB) has led to very few antibiotics being left for the treatment of human infections by multi-drug resistant bacteria. Despite extensive studies on carbapenem resistance (CR) in the healthcare setting, dissemination of CR outside the clinical environment has been less well characterised. This thesis first describes the occurrence of high-level CR in non-targeted Gram-positive bacteria, including the genera Staphylococcus and Enterococcus, in the public areas of a hospital. Further observation revealed that CR is spreading into a wide range of non-targeted Gram-negative bacteria, including 17 different genera and four phyla (Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes), which were found in coastal seawater and were likely introduced via terrestrial runoff water. Several of these non-targeted CRB, such as Staphylococcus haemolyticus, S. lugdunensis, Enterococcus faecalis, Stenotrophomonas maltophilia, Pseudomonas monteilii, P. fulva, Acinetobacter junii, A. johnsonii and Brevundimonas vesicularis, are considered to be human opportunistic pathogens. Their prevalence in coastal environments raises public health concerns. Further work in this thesis research addressed the molecular factors that underpin CR in environmental bacteria. CR in marine Rheinheimera isolates was found to be related to a novel Metallo beta-lactamase (MBL) gene (namely RH-B3-MBL), which probably has been horizontally transferred to the human opportunistic bacteria Citrobacter freundii and Enterobacter cloacae. This finding corroborates evidence showing that marine bacteria are a potential source of novel carbapenem resistance genes (CRG). A New Delhi Metallo beta-lactamase (NDM) gene (namely VR-NDM-1) was also identified in Variovorax isolates from the coastal runoff samples, and this gene was likely to have been acquired from Escherichia coli, Klebsiella pneumoniae or Acinetobacter baumannii. This finding shows that environmental bacteria can acquire CRGs from human-associated bacteria and then act as reservoirs for their further spread. The outcomes of this study will contribute to a better understanding of the role of the aquatic and marine environments in the spread of CRB outside the clinical setting