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Inhibition of the functional activity of Filamenting temperature-sensitive mutant Z (FtsZ) protein, an essential and highly conserved bacterial cytokinesis protein, is a promising approach for the development of a new class of antibacterial agents. Berberine, a benzylisoquinoline alkaloid widely used in traditional Chinese and native American medicines for its antimicrobial properties, has been recently reported to inhibit FtsZ. Using a combination of in silico structure-based design and in vitro biological assays, 9-phenoxyalkyl berberine derivatives were identified as potent FtsZ inhibitors. Compared to the parent compound berberine, the derivatives showed a significant enhancement of antibacterial activity against clinically relevant bacteria, and an improved potency against the GTPase activity and polymerization of FtsZ. The most potent compound 2 strongly inhibited the proliferation of Gram-positive bacteria, including methicillin-resistant S. aureus and vancomycin-resistant E. faecium, with MIC values between 2 and 4 µg/mL, and was active against the Gram-negative E. coli and K. pneumoniae, with MIC values of 32 and 64 µg/mL respectively. The compound perturbed the formation of cytokinetic Z-ring in E. coli. Also, the compound interfered with in vitro polymerization of S. aureus FtsZ. Taken together, the chemical modification of berberine with 9-phenoxyalkyl substituent groups greatly improved the antibacterial activity via targeting FtsZ.

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Multidrug resistant microbes present in the environment are a potential public health risk. In this study, we investigate the presence of New Delhi metallo-β-lactamase 1 (NDM-1) producing bacteria in the 99 water samples in Beijing City, including river water, treated drinking water, raw water samples from the pools and sewage from 4 comprehensive hospitals. For the bla NDM-1 positive isolate, antimicrobial susceptibility testing was further analyzed, and Pulsed Field Gel Electrophoresis (PFGE) was performed to determine the genetic relationship among the NDM-1 producing isolates from sewage and human, as well as the clinical strains without NDM-1. The results indicate that there was a higher isolation of NDM-1 producing Acinetobacter baumannii from the sewage of the hospitals, while no NDM-1 producing isolates were recovered from samples obtained from the river, drinking, or fishpond water. Surprisingly, these isolates were markedly different from the clinical isolates in drug resistance and pulsed field gel electrophoresis profiles, suggesting different evolutionary relationships. Our results showed that the hospital sewage may be one of the diffusion reservoirs of NDM-1 producing bacteria.

Background To investigate the carbapenem resistance mechanisms and clonal relationship of carbapenem-resistant Acinetobacter baumannii (CRAB) strains isolated in the intensive care unit (ICU) of the First Affiliated Hospital of Jiamusi University, management approaches to ICU clonal CRAB outbreaks were described. Methods The sensitivity of the antibiotic was determined using the VITEK-2 automated system. Carbapenemase genes ( bla TEM , bla SHV , bla KPC , bla NDM , bla IMP-4 , bla VIM , bla OXA-23 , bla OXA-24 , bla OXA-51 , and bla OXA-58 ), AmpC enzyme genes ( bla ACC , bla DHA , bla ADC ), and ISAba1 were assessed for all collected isolates using polymerase chain reaction (PCR). The transfer of resistance genes was investigated via conjugation experiments. The clonal relationship of isolates was determined via enterobacterial repetitive intergenic consensus (ERIC)-PCR and multilocus sequence typing (MLST). When the detection rate of CRAB increased from 25% in 2010 to 92% in 2014, a number of actions were initiated, including enhanced infection control, staff education, and the cleaning of the hospital environment. Results Clinical isolates were positive for the following genes: bla OXA23 , bla OXA51 , bla OXA24 , bla ADC , bla TEM , ISAba1 , ISA-23 , and ISA-ADC ; however, bla OXA58 , ISA-51 , bla NDM , bla IMP , bla KPC , bla TEM , bla SHV , bla VIM , and bla ACC were not detected. Four carbapenem-resistant isolates successfully transferred plasmids from A. baumannii isolates to E. coli J53. MLST showed that all strains belonged to ST2 except for one isolate, which belonged to the new genotype ST1199. The ERIC-PCR method fou...

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Background: Carbapenem-resistant hypervirulent Klebsiella pneumoniae strains have recently come into existence worldwide; however, researchers in northeast China are not aware of their clinical features and molecular characteristics. Methods: Here, the molecular and virulent characteristics of 44 carbapenem-resistant K. pneumoniae (CRKP) isolates collected from January 2015 to December 2017 were studied. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were carried out to define the clonal relatedness among the isolates. PCR and capsular serotyping of the virulence-associated genes, as well as biofilm formation and serum complement-mediated killing assays, were employed to determine the virulent potential. The genomic features and associated mobile genetic elements of JmsCRE57 were detected by whole genome sequencing. Results: The only positive isolate was JmsCRE57, which belonged to the ST375 serotype K2 that expressed uge, mrkD, fimH, kpn, aerobactin and rmpA virulence-associated genes and showed strong biofilm formation and serum sensitivity. Sequencing results showed that the JmsCRE57 genome mainly consisted of a circular chromosome, three antimicrobial resistant plasmids and a virulent plasmid. The antimicrobial resistant plasmid expressing bla KPC-2 , bla CTX-M-15 , aph(3″)-Ib, aph(6)-Id, qnrB1, aac(3)-IIa, aac(6′)-Ib-cr, bla OXA-1 , bla TEM-1B , catB4, sul2, dfrA14 and bla SHV-99. The virulent plasmid belonged to the IncHI1B group, which is mainly composed of mucoid phenotype genes and siderophore-associated genes. The remaining CRKP strains that expressed uge, fimH, mrkD and kpn virulenceassociated genes were not successfully typed.