Inflammation plays an important role in cardiac dysfunction under different situations. Acute systemic inflammation occurring in patients with severe

Acinetobacter baumannii has emerged as one of the most important hospital-acquired pathogens in the world, because of its resistance to almost all available antibiotic drugs. Endolysins from phages are attracting increasing interest as potential antimicrobial agents, especially for drug-resistant bacteria. We previously isolated and characterized Abp1, a virulent phage targeting the multidrug-resistant A. baumannii strain, AB1. To evaluate the antimicrobial potential of endolysin from the Abp1 phage, the endolysin gene plyAB1 was cloned and over-expressed in Escherichia coli, and the lytic activity of the recombinant protein (PlyAB1) was tested by turbidity assessment and bacteria counting assays. PlyAB1 exhibits a marked lytic activity against A. baumannii AB1, as shown by a decrease in the number of live bacteria following treatment with the enzyme. Moreover, PlyAB1 displayed a highly specific lytic effect against all of the 48 hospital-derived pandrug-resistant A. baumannii isolates that were tested. These isolates were shown to belong to different ST clones by multilocus sequence typing. The results presented here show that PlyAB1 has potential as an antibiotic against drug-resistant A. baumannii.

Acinetobacter baumannii is a growing threat, although lytic bacteriophages have been shown to effectively kill A. baumannii. However, the interaction between the host and the phage has not been fully studied. We demonstrate the global profile of transcriptional changes in extensively drug-resistant A. baumannii AB1 and the interaction with phage φAbp1 through RNA sequencing (RNA-seq) and bioinformatic analysis. Only 15.6% (600/3,838) of the genes of the infected host were determined to be differentially expressed genes (DEGs), indicating that only a small part of the bacterial resources was needed for φAbp1 propagation. Contrary to previous similar studies, more upregulated rather than downregulated DEGs were detected. Specifically, φAbp1 infection caused the most extensive impact on host gene expression at 10 min, which was related to the intracellular accumulation phase of virus multiplication. Based on the gene coexpression network, a middle gene (gp34, encoding phage-associated RNA polymerase) showed a negative interaction with numerous host ribosome protein genes. In addition, the gene expression of bacterial virulence/resistance factors was proven to change significantly. This work provides new insights into the interactions of φAbp1 and its host, which contributes to the further understanding of phage therapy, and provides another reference for antibacterial agents. IMPORTANCE Previous research has reported the transcriptomic phage-host interactions in Escherichia coli and Pseudomonas aeruginosa, leading to the detailed discovery of transcriptomic regulations and predictions of specific gene functions. However, a direct relationship between A. baumannii and its phage has not been previously reported, although A. baumannii is becoming a rigorous drug-resistant threat. We analyzed transcriptomic changes after φAbp1 infected its host, extensively drug-resistant (XDR) A. baumannii AB1, and found defense-like responses of the host, step-by-step control by the invader, elaborate interactions between host and phage, and elevated drug resistance gene expressions of AB1 after phage infection. These findings suggest the detailed interactions of A. baumannii and its phage, which may provide both encouraging suggestions for drug design and advice for the clinical use of vital phage particles.

Pseudomonas aeruginosa is the leading cause of infection in burn patients. The increasing carbapenem resistance of P. aeruginosa has become a serious challenge to clinicians. The present study investigated the molecular typing and carbapenem resistance mechanisms of 196 P. aeruginosa isolates from the bloodstream and wound surface of patients in our burn center over a period of 6 years. By multilocus sequence typing (MLST), a total of 58 sequence types (STs) were identified. An outbreak of ST111, a type that poses a high international risk, occurred in 2014. The isolates from wound samples of patients without bacteremia were more diverse and more susceptible to antibiotics than strains collected from the bloodstream or the wound surface of patients with bacteremia. Importantly, a large proportion of the patients with multisite infection (46.51%) were simultaneously infected by different STs in the bloodstream and wound surface. Antimicrobial susceptibility testing of these isolates revealed high levels of resistance to carbapenems, with 35.71% susceptibility to imipenem and 32.14% to meropenem. To evaluate mechanisms associated with carbapenem resistance, experiments were conducted to determine the prevalence of carbapenemase genes, detect alterations of the oprD porin gene, and measure expression of the ampC β-lactamase gene and the mexB multidrug efflux gene. The main mechanism associated with carbapenem resistance was mutational inactivation of oprD (88.65%), accompanied by overexpression of ampC (68.09%). In some cases, oprD was inactivated by insertion sequence element IS1411, which has not been found previously in P. aeruginosa. These findings may help control nosocomial P. aeruginosa infections and improve clinical practice.

The mechanism underlying pulmonary inflammation in thermal inhalation injury remains elusive. Cystic fibrosis, also hallmarked with pulmonary inflammation, is caused by mutations in CFTR, the expression of which is temperature-sensitive. We investigated whether CFTR is involved in heat-induced pulmonary inflammation. We applied heat-treatment in 16HBE14o- cells with CFTR knockdown or overexpression and heat-inhalation in rats in vivo. Heat-treatment caused significant reduction in CFTR and, reciprocally, increase in COX-2 at early stages both in vitro and in vivo. Activation of ERK/JNK, NF-κB and COX-2/PGE₂ were detected in heat-treated cells, which were mimicked by knockdown and reversed by overexpression of CFTR or VX-809, a reported CFTR mutation corrector. JNK/ERK inhibition reversed heat-/CFTR-knockdown-induced NF-κB activation, whereas NF-κB inhibitor showed no effect on JNK/ERK. IL-8 was augmented by heat-treatment or CFTR-knockdown, which was abolished by inhibition of NF-κB, JNK/ERK or COX-2. Moreover, in vitro or in vivo treatment with curcumin, a natural phenolic compound, significantly enhanced CFTR expression and reversed the heat-induced increases in COX-2/PGE₂/IL-8, neutrophil infiltration and tissue damage in the airway. These results have revealed a CFTR-regulated MAPK/NF-κB pathway leading to COX-2/PGE₂/IL-8 activation in thermal inhalation injury and demonstrated therapeutic potential of curcumin for alleviating heat-induced pulmonary inflammation.