The Rhizome of the Multidrug-Resistant Enterobacter aerogenes Genome Reveals How New “Killer Bugs” Are Created because of a Sympatric Lifestyle

Abstract

Here, we sequenced the 5,419,609 bp circular genome of an Enterobacter aerogenes clinical isolate that killed a patient and was resistant to almost all current antibiotics (except gentamicin) commonly used to treat Enterobacterial infections, including colistin. Genomic and phylogenetic analyses explain the discrepancies of this bacterium and show that its core genome originates from another genus, Klebsiella. Atypical characteristics of this bacterium (i.e., motility, presence of ornithine decarboxylase, and lack of urease activity) are attributed to genomic mosaicism, by acquisition of additional genes, such as the complete 60,582 bp flagellar assembly operon acquired "en bloc" from the genus Serratia. The genealogic tree of the 162,202 bp multidrug-resistant conjugative plasmid shows that it is a chimera of transposons and integrative conjugative elements from various bacterial origins, resembling a rhizome. Moreover, we demonstrate biologically that a G53S mutation in the pmrA gene results in colistin resistance. E. aerogenes has a large RNA population comprising 8 rRNA operons and 87 cognate tRNAs that have the ability to translate transferred genes that use different codons, as exemplified by the significantly different codon usage between genes from the core genome and the "mobilome." On the basis of our findings, the evolution of this bacterium to become a "killer bug" with new genomic repertoires was from three criteria that are "opportunity, power, and usage" to indicate a sympatric lifestyle: "opportunity" to meet other bacteria and exchange foreign sequences since this bacteria was similar to sympatric bacteria; "power" to integrate these foreign sequences such as the acquisition of several mobile genetic elements (plasmids, integrative conjugative element, prophages, transposons, flagellar assembly system, etc.) found in his genome; and "usage" to have the ability to translate these sequences including those from rare codons to serve as a translator of foreign languages.

Whole-Genome Sequence of Chryseobacterium oranimense, a Colistin-Resistant Bacterium Isolated from a Cystic Fibrosis Patient in France

“…In K. pneumoniae, the resistance to polymyxin is due to increased production of capsular polysaccharides (61). Recently, it has been demonstrated that in Acinetobacter baumannii or in Enterobacter aerogenes, acquired resistance to colistin may also be due to mutations in the pmrA-pmrB two-component systems (62,63). Finally loss of LPS production by mutations in the three genes lpxA, lpxC, and lpxD has been associated with the resistance to Acinetobacter baumannii (64).…”

Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

“…Polymyxin Activity, Susceptibility, and Resistance Clinical Microbiology Reviews ter aerogenes (121), and Salmonella enterica (122,123) (Table 3). These mutations are responsible for constitutive activation of the PmrAB two-component system, leading to upregulation of the pmrCAB operon, the pmrHFIJKLM operon, and the pmrE gene, and thus to the synthesis of pEtN and L-Ara4N and their transfer to lipid A (Fig.…”

Environmental Shaping of Codon Usage and Functional Adaptation Across Microbial Communities

“…We speculate that the intercommunity CU bias we observe may be a consequence of an extensive exchange of genetic information in an environment, up to and including the level that is the strongest selection force for CU optimization-the shared tRNA pool (57,58). This in turn can be considered beneficial in particular for lifestyle-specific genes.…”