Journal Articles

Permanent URI for this collectionhttps://mro.massey.ac.nz/handle/10179/7915

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Author: search.filters.author.Nisa SSubject: search.filters.subject.1108 Medical Microbiology

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    Targeting the chromosome partitioning protein ParA in tuberculosis drug discovery.
    (2010-11) Nisa S; Blokpoel MCJ; Robertson BD; Tyndall JDA; Lun S; Bishai WR; O'Toole R
    OBJECTIVE: To identify inhibitors of the essential chromosome partitioning protein ParA that are active against Mycobacterium tuberculosis. METHODS: Antisense expression of the parA orthologue MSMEG_6939 was induced on the Mycobacterium smegmatis background. Screening of synthetic chemical libraries was performed to identify compounds with higher anti-mycobacterial activity in the presence of parA antisense. Differentially active compounds were validated for specific inhibition of purified ParA protein from M. tuberculosis (Rv3918c). ParA inhibitors were then characterized for their activity towards M. tuberculosis in vitro. RESULTS: Under a number of culture conditions, parA antisense expression in M. smegmatis resulted in reduced growth. This effect on growth provided a basis for the detection of compounds that increased susceptibility to expression of parA antisense. Two compounds identified from library screening, phenoxybenzamine and octoclothepin, also inhibited the in vitro ATPase activity of ParA from M. tuberculosis. Structural in silico analyses predict that phenoxybenzamine and octoclothepin undergo interactions compatible with the active site of ParA. Octoclothepin exhibited significant bacteriostatic activity towards M. tuberculosis. CONCLUSIONS: Our data support the use of whole-cell differential antisense screens for the discovery of inhibitors of specific anti-tubercular drug targets. Using this approach, we have identified an inhibitor of purified ParA and whole cells of M. tuberculosis.
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    Diverse Epidemiology of Leptospira serovars Notified in New Zealand, 1999-2017
    (MDPI (Basel, Switzerland), 14/10/2020) Nisa S; Wilkinson DA; Angelin-Bonnet O; Paine S; Cullen K; Wight J; Baker MG; Benschop J
    Leptospirosis in New Zealand has been strongly associated with animal-contact occupations and with serovars Hardjo and Pomona. However, recent data suggest changes in these patterns, hence, serovar-specific epidemiology of leptospirosis from 1999 to 2017 was investigated. The 19-year average annual incidence is 2.01/100,000. Early (1999-2007) and late (2008-2017) study period comparisons showed a significant increase in notifications with serovar Ballum (IRR: 1.59, 95% CI: 1.22-2.09) in all cases and serovar Tarassovi (IRR: 1.75, 95% CI: 1.13-2.78) in Europeans and a decrease in notifications with serovars Hardjo and Pomona in all cases. Incidences of Ballum peaked in winter, Hardjo peaked in spring and Tarassovi peaked in summer. Incidence was highest in Māori (2.24/100,000) with dominant serovars being Hardjo and Pomona. Stratification by occupation showed meat workers had the highest incidence of Hardjo (57.29/100,000) and Pomona (45.32/100,000), farmers had the highest incidence of Ballum (11.09/100,000) and dairy farmers had the highest incidence of Tarassovi (12.59/100,000). Spatial analysis showed predominance of Hardjo and Pomona in Hawke's Bay, Ballum in West Coast and Northland and Tarassovi in Waikato, Taranaki and Northland. This study highlights the serovar-specific heterogeneity of human leptospirosis in New Zealand that should be considered when developing control and prevention strategies.