Polymyxin-based fluorescent probes to combat Gram-negative antimicrobial resistance.

Reliable diagnostic approaches especially those targeting critical Gram-negative bacteria are urgently needed for the prevention of antimicrobial resistance. Polymyxin B (PMB) which specifically targets the outer membrane of Gram-negative bacteria is the last-line antibiotic against life-threatening multidrug-resistant Gram-negative bacteria. However, increasing number of studies have reported the spread of PMB-resistant strains. With the aim to specifically detect Gram-negative bacteria and potentially reduce the irrational use of antibiotics, we herein rationally designed two Gram-negative bacteria specific fluorescent probes based on our previous activity-toxicity optimization of PMB. The in vitro probe PMS-Dns showed fast and selective labeling of Gram-negative pathogens in complex biological cultures. Subsequently, we constructed the caged in vivo fluorescent probe PMS-Cy-NO2 by conjugating bacterial nitroreductase (NTR)-activatable positive charged hydrophobic near-infrared (NIR) fluorophore with polymyxin scaffold. Significantly, PMS-Cy-NO2 exhibited excellent Gram-negative bacterial detection capability with the differentiation between Gram-positive and Gram-negative in a mouse skin infection model.

Design, Synthesis, and Bioactivity Investigation of Cyclic Lipopeptide Antibiotics Containing Eight to Nine Amino Acids.

The current global issue of antibiotic resistance is serious, and there is an urgent requirement of developing novel antibiotics. Octapeptins have recently regained interest because of their activities against resistant Gram-negative bacteria. We synthesized four natural octapeptins and 33 derivatives with diverse polarity, amphiphilicity, and acid-base properties by solid-phase synthesis and investigated their in vitro antibacterial activity and renal cytotoxicity. We also assessed the structure-activity relationship and structure-toxicity relationship of the cyclic lipopeptide compounds. Some compounds showed increased activity against Gram-negative and/or Gram-positive bacteria, with improved renal cytotoxicity. C-02 showed remarkable in vitro antibacterial activity and low renal cytotoxicity. We found that C-02 showed high antibacterial activity against Escherichia coli in vivo and manifested its effects preliminarily by increasing outer membrane permeability. Therefore, C-02 might be a new antibiotic lead compound with not only high efficacy but also low renal cytotoxicity.

[Malaria Incidence and Control in Baoshan City during the Twelfth Five-Year Plan Period].

A retrospective analysis was made on malaria incidence in Baoshan City of Yunnan Province during the 2011-2015 Twelfth Five-Year Plan Period. The epidemiological characteristics and endemic situation of malaria were analyzed. A total of 1 301 malaria cases were reported in Baoshan City during 2011-2015, with an average incidence rate of 10.2 per 100 000 individuals, showing a relatively low prevelence of malaria. The cases were mostly imported（98.5%, 1 282/1 301）. No local malaria cases were found in Baoshan City since 2014. The cases were mostly in Tengchong City（65.6%, 853/1 301）, and mainly in the age range of 20-50 years （84.4%, 1 098/1 301）.

[Analysis of Time Distribution of Malaria Incidence in Baoshan City During 1990-2014].

The malaria epidemic data in Baoshan city from 1990 to 2014 were analyzed with concentration ratio and circular distribution. Results showed that the incidence of malaria in Baoshan city displayed a trend of decrease from 1990 to 2014. The total concentration ration M was 0.36, the circular distribution r was 0.30, and the average angle α was 148.78°. The malaria incidence peaked on May 31, with the epidemic period being from March 2 to August 29, which is inconsistent with the seasonal ebb and flow of local malaria vector.