Chemical inhibition of bacterial protein tyrosine phosphatase suppresses capsule production

Capsule polysaccharide is a major virulence factor for a wide range of bacterial pathogens, including Streptococcus pneumoniae. The biosynthesis of Wzy-dependent capsules in both Gram-negative and –positive bacteria is regulated by a system involving a protein tyrosine phosphatase (PTP) and a protein tyrosine kinase. However, how the system functions is still controversial. In Streptococcus pneumoniae, a major human pathogen, the system is present in all but 2 of the 93 serotypes found to date. In order to study this regulation further, we performed a screen to find inhibitors of the phosphatase, CpsB. This led to the observation that a recently discovered marine sponge metabolite, fascioquinol E, inhibited CpsB phosphatase activity both in vitro and in vivo at concentrations that did not affect the growth of the bacteria. This inhibition resulted in decreased capsule synthesis in D39 and Type 1 S. pneumoniae. Furthermore, concentrations of Fascioquinol E that inhibited capsule also lead to increased attachment of pneumococci to a macrophage cell line, suggesting that this compound would inhibit the virulence of the pathogen. Interestingly, this compound also inhibited the phosphatase activity of the structurally unrelated Gram-negative PTP, Wzb, which belongs to separate family of protein tyrosine phosphatases. Furthermore, incubation with Klebsiella pneumoniae¸ which contains a homologous phosphatase, resulted in decreased capsule synthesis. Taken together, these data provide evidence that PTPs are critical for Wzydependent capsule production across a spectrum of bacteria, and as such represents a valuable new molecular target for the development of anti-virulence antibacterials.Alistair J. Standish, Angela A. Salim, Hua Zhang, Robert J. Capon and Renato Moron

Climate change mitigation potential in sanitation via off-site composting of human waste

Approximately 4.5 billion people lack access to safely managed sanitation globally, and 1 billion live in slums, often relying on anaerobic waste containment in pit latrines. Providing access to safely managed sanitation may lead to reduced GHG emissions and thus simultaneously address both Sustainable Development Goals. Here we measure cumulative GHG emissions of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) during the off-site composting of human waste to estimate scalable emission factors. We find that CH4 emission factors are one to two orders of magnitude smaller than IPCC values for other excreta collection, treatment and disposal processes. After accounting for GHG emissions throughout the sanitation cycle, including transport, urine and compost end-use, the climate change mitigation potential is 126 kg of CO2-equivalent per capita per year for slum inhabitants. If scaled to global slum populations, composting could mitigate 3.97 Tg CH4 yr−1, representing 13-44% of sanitation sector CH4 emissions