Complete genome sequence and analysis of the multiresistant nosocomial pathogen Corynebacterium jeikeium K411, a lipid-requiring bacterium of the human skin flora

Abstract

Corynebacterium jeikeium is a "lipophilic" and multidrug-resistant bacterial species of the human skin flora that has been recognized with increasing frequency as a serious nosocomial pathogen. Here we report the genome sequence of the clinical isolate C. jeikeium K411, which was initially recovered from the axilla of a bone marrow transplant patient. The genome of C. jeikeium K411 consists of a circular chromosome of 2,462,499 bp and the 14,323-bp bacteriocin-producing plasmid pKW4. The chromosome of C. jeikeium K411 contains 2,104 predicted coding sequences, 52% of which were considered to be orthologous with genes in the Corynebacterium glutamicum, Corynebacterium efficiens, and Corynebacterium diphtheriae genomes. These genes apparently represent the chromosomal backbone that is conserved between the four corynebacteria. Among the genes that lack an ortholog in the known corynebacterial genomes, many are located close to transposable elements or revealed an atypical G+C content, indicating that horizontal gene transfer played an important role in the acquisition of genes involved in iron and manganese homeostasis, in multidrug resistance, in bacterium-host interaction, and in virulence. Metabolic analyses of the genome sequence indicated that the "lipophilic" phenotype of C. jeikeium most likely originates from the absence of fatty acid synthase and thus represents a fatty acid auxotrophy. Accordingly, both the complete gene repertoire and the deduced lifestyle of C. jeikeium K411 largely reflect the strict dependence of growth on the presence of exogenous fatty acids. The predicted virulence factors of C. jeikeium K411 are apparently involved in ensuring the availability of exogenous fatty acids by damaging the host tissue.

FIG. 1.

Circular representation of the C. jeikeium K411 chromosome. From the outer circle to the inner circle: circle 1, DNA base pair numbers; circles 2 and 3, genes transcribed clockwise and counterclockwise, respectively (genes are marked according to the assigned COG classes [72]); circle 4, genes involved in fatty acid metabolism (blue) and in iron and manganese homeostasis (orange); circle 5, genes potentially involved in multidrug resistance (green) and predicted virulence factors (red); circle 6, insertion sequences; circle 7, G+C content with values positively deviating from the median shown in black; circle 8, GC skew. The G+C content and GC skew were calculated within a 3,000-bp window along with a sliding window of 1,000 bp.

FIG. 2.

Synteny between the C. jeikeium K411 genome and the C. glutamicum ATCC 13032, C. efficiens YS-314, and C. diphtheriae NCTC 13129 genomes. The diagram shows x-y plots of dots forming syntenic regions between the corynebacterial genomes. Each dot represents a C. jeikeium CDS having an ortholog in another corynebacterial genome, with coordinates corresponding to the CDS number in each genome. The orthologs were identified by best BLASTP matches of amino acid sequences deduced from CDS 2104 of the C. jeikeium K411 chromosome with proteins encoded by C. glutamicum (CDS 3002; red dots), C. efficiens (CDS 2950; green), and C. diphtheriae (CDS 2320, blue). Apparent breakpoints in synteny revealing genomic inversions in the C. jeikeium K411 chromosome are specifically marked by arrows 1 to 4. Differences in synteny originating from DNA translocation are indicated by pairs of vertical and horizontal arrows (arrows 5). Additionally, the position of an apparent insertion of DNA in the C. jeikeium K411 genome (jk1226 to jk1265) is shown (arrow 6).

FIG. 3.

Overview of prominent metabolic and medically relevant features of C. jeikeium K411 deduced from the complete genome sequence. Processes and relevant proteins associated primarily with carbohydrate metabolism (yellow), fatty acid metabolism (blue), iron and manganese uptake (orange), antibiotic efflux (green), and virulence (red) are indicated. Putative transport systems are shown within the cell membrane; the numbers in parentheses indicate the approximate numbers of each type. Structural elements of ABC transporters are depicted as circles for membrane-spanning permeases and diamonds for nucleotide-binding proteins; other transporters are drawn as ovals. Major metabolic pathways are shown in the center of the cell; the numbers in parentheses indicate the numbers of paralogous genes present in the C. jeikeium K411 genome. Prominent proteins most likely secreted by the machinery of the general secretory (sec) pathway are shown on the right, along with sortase (SrtA) processed proteins and a predicted collagen adhesin (CbpA), which are anchored to the cell wall. The putative membrane-damaging role of the predicted virulence factors, ensuring the availability of exogenous fatty acids for growth of C. jeikeium, is indicated.