This is probably the first reported outbreak of multidrug/carbapenem-resistant Klebsiella infection involving the OXA-48 gene from Saudi Arabia. Although the presence of ESBLs such as OXA, CTX-M, TEM, and SHV are predictable reasons for resistance, variations in the Omp-36 gene might also have precipitated this phenomenon. Disruption of the Omp-36 sequence by large insertional elements, the insertion of two amino acids in a very crucial part of this protein, and the presence of a premature stop codon in one isolate might have rendered this protein incomplete and non-functional. The study also demonstrated that more than one type of clone was responsible for this reported apparent outbreak and that ST29, a clone not reported from this region before, was the major clone responsible.

BackgroundThe nexus between resistance determinants, plasmid type, and clonality appears to play a crucial role in the dissemination and survival of carbapenem-resistant Klebsiella pneumoniae (CRKP). The incidence of infections involving CRKP in Saudi Arabia is increasing and there is a need for detailed molecular profiling of this pathogen for CRKP surveillance and control.MethodsThe resistance determinants of 71 non-redundant CRKP isolates were investigated by polymerase chain reaction (PCR) and sequencing. Plasmid typing was performed using PCR-based replicon typing and the clonality of isolates was determined by multilocus sequence typing. Capsular polysaccharide synthesis genes and other virulence factors were examined using multiplex PCR. Diversity was calculated using DIVEIN, clonal relationship was determined using eBURST, and phylogenetic analysis was performed using SplitsTree4.ResultsA polyclonal OXA-48 gene alone was the most common carbapenemase detected in 48/71 (67.6%) isolates followed by NDM-1 alone in 9/71 (12.7%) isolates. Coproduction of OXA-48 and NDM-1 was observed in 6/71 (8.5%) isolates. Both carbapenemase genes could be transferred into an Escherichia coli recipient. CTX-M-15 was the most abundant extended-spectrum β-lactamase gene detected in 47/71 (66.2%) isolates, whereas clone-specific CTX-M-14 (ST-199 and -709) was found in 15/71 (21%) isolates. Sixty-seven of 71 isolates were positive for one or more plasmid replicons. The replicons detected were: IncFII; IncFIIK; IncFIA; IncFIB; L/M; IncI1; and IncN. FIIK and L/M were predominant, with 69 and 67% positivity, respectively. All isolates were negative for the magA (K1), rmpA, and K2 genes and presented a non-hypermucoviscous phenotype.ConclusionA polyclonal CRKP reservoir of sequence types (STs)-37, − 199, and − 152 was observed and ST-152 appeared to be a “frequent carrier” of the NDM-1 gene. ST-199, a singleton not previously reported, showed a sequence diversity suggestive of positive selection. A significant association was evident between resistance determinants and the clonal types of K. pneumoniae: all ST-152 isolates were positive for NDM-1 but negative for OXA-48; ST-199 isolates were positive for OXA-48 but negative for NDM-1; and ST-709 and -199 isolates were positive for CTX-M-14. The incidence of certain clonal types in large numbers predicts an outbreak-like situation and warrants stringent surveillance and infection control.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3114-9) contains supplementary material, which is available to authorized users.

Colorectal cancer is the third most incidental cancer worldwide, and the response rate of current treatment for colorectal cancer is very low. Genome-scale metabolic models (GEMs) are systems biology platforms, and they had been used to assist researchers in understanding the metabolic alterations in different types of cancer. Here, we reconstructed a generic colorectal cancer GEM by merging 374 personalized GEMs from the Human Pathology Atlas and used it as a platform for systematic investigation of the difference between tumor and normal samples. The reconstructed model revealed the metabolic reprogramming in glutathione as well as the arginine and proline metabolism in response to tumor occurrence. In addition, six genes including ODC1, SMS, SRM, RRM2, SMOX, and SAT1 associated with arginine and proline metabolism were found to be key players in this metabolic alteration. We also investigated these genes in independent colorectal cancer patients and cell lines and found that many of these genes showed elevated level in colorectal cancer and exhibited adverse effect in patients. Therefore, these genes could be promising therapeutic targets for treatment of a specific colon cancer patient group.