RepoMan is a scaffold for signalling by mitotic phosphatases at the chromosomes. During (pro)metaphase, RepoMan-associated protein phosphatases PP1 and PP2A-B56 regulate the chromosome targeting of Aurora-B kinase and RepoMan, respectively. Here we show that this task division is critically dependent on the phosphorylation of RepoMan by protein kinase Cyclin-dependent kinase 1 (Cdk1), which reduces the binding of PP1 but facilitates the recruitment of PP2A-B56. The inactivation of Cdk1 in early anaphase reverses this phosphatase switch, resulting in the accumulation of PP1-RepoMan to a level that is sufficient to catalyse its own chromosome targeting in a PP2A-independent and irreversible manner. Bulk-targeted PP1-RepoMan also inactivates Aurora B and initiates nuclear-envelope reassembly through dephosphorylation-mediated recruitment of Importin β. Bypassing the Cdk1 regulation of PP1-RepoMan causes the premature dephosphorylation of its mitotic-exit substrates in prometaphase. Hence, the regulation of RepoMan-associated phosphatases by Cdk1 is essential for the timely dephosphorylation of their mitotic substrates.

Background Colistin resistance mediated by mcr-1 -harbouring plasmids is an emerging threat in Enterobacteriaceae, like Salmonella . Based on its major contribution to the diarrhoea burden, the epidemic state and threat of mcr-1 -harbouring Salmonella in community-acquired infections should be estimated. Methods This retrospective study analysed the mcr-1 gene incidence in Salmonella strains collected from a surveillance on diarrhoeal outpatients in Shanghai Municipality, China, 2006–2016. Molecular characteristics of the mcr-1 -positive strains and their plasmids were determined by genome sequencing. The transfer abilities of these plasmids were measured with various conjugation strains, species, and serotypes. Findings Among the 12,053 Salmonella isolates, 37 mcr-1 -harbouring strains, in which 35 were serovar Typhimurium, were detected first in 2012 and with increasing frequency after 2015. Most patients infected with mcr-1 -harbouring strains were aged <5 years. All strains, including fluoroquinolone-resistant and/or extended-spectrum β-lactamase-producing strains, were multi-drug resistant. S. Typhimurium had higher mcr-1 plasmid acquisition ability compared with other common serovars. Phylogeny based on the genomes combined with complete plasmid sequences revealed some clusters, suggesting the presence of mcr-1 -harbouring Salmonella outbreaks in the community. Most mcr-1 -positive strains were clustered together with the pork strains, strongly suggesting pork consumption as a main infection source. Interpretation The mcr-1 -harbouring Salmonella prevalence in community-acquired diarrhoea displays a rapid increase trend, and the ESBL -mcr-1 -harbouring Salmonella poses a threat for children. These findings highlight the necessary and significance of prohibiting colistin use in animals and continuous monitoring of mcr-1 -harbouring Salmonella .

We conducted a retrospective study on non-typhoidal Salmonella isolates from patients with diarrhoea in Shanghai, China, 2006-2010. A total of 1484 isolates of 70 Salmonella serovars were recovered from about 18 000 stool specimens. Serovars Enteritidis and Typhimurium were the most prevalent with isolation rates of 27.6% and 25.5%, respectively. The majority (1151, 77.6%) of the isolates were resistant to at least one antimicrobial, and 598 (40.3%) to more than three antimicrobials. Approximately half (50.9%) of the isolates were resistant to nalidixic acid and other resistance rates were sulfisoxazole (47.9%), streptomycin (37.6%), ampicillin (31.3%) and tetracycline (30.5%). Co-resistance to fluoroquinolones and the third- and fourth-generation cephalosporins was also identified.

We identified 2912 Shigella isolates from diarrhoeal patients in China during 2003-2013. The most common species was Shigella flexneri (55.3%), followed by Shigella sonnei (44.1%); however, S. sonnei is becoming increasingly prevalent. Among the S. flexneri isolates, serotypes 2a and X variant (-:7,8, E1037) were the two most prevalent serotypes, and serologically atypical isolates were also commonly identified. Overall, S. sonnei, S. flexneri 2a and S. flexneri X variant (-:7,8, E1037) accounted for 76.1% of all Shigella isolates, and their prevalence increased from 54.0% during 2003-2004 to 84.1% during 2011-2013. A change was observed in the serotype distribution of Shigella in China during this period, and we propose an ideal strategy to inform the development of a broadly effective Shigella vaccine candidate.