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Carbapenem-resistant Klebsiella pneumoniae (CRKP) are usually multidrug resistant (MDR) and cause serious therapeutic problems. Colistin is a critical last-resort therapeutic option for MDR bacterial infections. However, increasing colistin use has led to the emergence of extensively drug-resistant (XDR) strains, raising a significant challenge for healthcare. In order to gain insight into the antibiotic resistance mechanisms of CRKP and identify potential drug targets, we compared the molecular characteristics and the proteomes among drug-sensitive (DS), MDR, and XDR K. pneumoniae strains. All drug-resistant isolates belonged to ST11, harboring blaKPC and hypervirulent genes. None of the plasmid-encoded mcr genes were detected in the colistin-resistant XDR strains. Through a tandem mass tag (TMT)-labeled proteomic technique, a total of 3531 proteins were identified in the current study. Compared to the DS strains, there were 247 differentially expressed proteins (DEPs) in the MDR strains and 346 DEPs in the XDR strains, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that a majority of the DEPs were involved in various metabolic pathways, which were beneficial to the evolution of drug resistance in K. pneumoniae. In addition, a total of 67 DEPs were identified between the MDR and XDR strains. KEGG enrichment and protein–protein interaction network analysis showed their participation in cationic antimicrobial peptide resistance and two-component systems. In conclusion, our results highlight the emergence of colistin-resistant and hypervirulent CRKP, which is a noticeable superbug. The DEPs identified in our study are of great significance for the exploration of effective control strategies against infections of CRKP.

Long non‐coding ribonucleic acids (lncRNAs) play critical roles in acute lung injury (ALI). We aimed to explore the involvement of lncRNA HOX transcript antisense intergenic ribonucleic acid (HOTAIR) in regulating autophagy in lipopolysaccharide (LPS)‐induced ALI. We obtained 1289 differentially expressed lncRNAs or messenger RNAs (mRNAs) via microarray analysis. HOTAIR was significantly upregulated in the LPS stimulation experimental group. HOTAIR knockdown (si‐HOTAIR) promoted cell proliferation in LPS‐stimulated A549 and BEAS‐2B cells, suppressing the protein expression of autophagy marker light chain 3B and Beclin‐1. Inhibition of HOTAIR suppressed LPS‐induced cell autophagy, apoptosis and arrested cells in the G0/G1 phase prior to S phase entry. Further, si‐HOTAIR alleviated LPS‐induced lung injury in vivo. We predicted the micro‐ribonucleic acid miR‐17‐5p to target HOTAIR and confirmed this via RNA pull‐down and dual luciferase reporter assays. miR‐17‐5p inhibitor treatment reversed the HOTAIR‐mediated effects on autophagy, apoptosis, cell proliferation and cell cycle. Finally, we predicted autophagy‐related genes (ATGs) ATG2, ATG7 and ATG16 as targets of miR‐17‐5p, which reversed their HOTAIR‐mediated protein upregulation in LPS‐stimulated A549 and BEAS‐2B cells. Taken together, our results indicate that HOTAIR regulated apoptosis, the cell cycle, proliferation and autophagy through the miR‐17‐5p/ATG2/ATG7/ATG16 axis, thus driving LPS‐induced ALI.