Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

Objective To evaluate the effect of schistosomiasis control in Yunnan Province since achieving the transmission control standards,so as to provide the evidence for formulating the next prevention and control strategy. Methods The schistoso-miasis epidemic monitoring reports,annual reports,relevant information about Oncomelania hupensis snails,and schistosomiasis patient conditions were collected and analyzed for epidemic condition and characteristics of schistosomiasis in Yunnan Province from 2009 to 2012. Results The various epidemic monitoring indicators all decreased. In 2012,compared with 2009,the preva-lence reduced by 33.33%after correction;the number of villages with schistosomiasis patients reduced by 55.56%;the adjusted positive rate of livestock stool tests reduced by 45.45%;the number of villages with infected cow reduced by 42.25%;the actual area with snails reduced by 13.58%;the density of living snails reduced by 25.66%,and no schistosome infected snails were found in 2012. Conclusion There still exist schistosome infections in human and animals in some local areas of Yunnan Prov-ince,and it is difficult to achieve the standard of schistosomiasis transmission interrupted in a short period.