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Independent component analysis reveals 49 independently modulated gene sets within the global transcriptional regulatory architecture of multidrug-resistant Acinetobacter baumannii.
Acinetobacter baumannii causes severe infections in humans, resists multiple antibiotics, and survives in stressful environmental conditions due to modulations of its complex transcriptional regulatory network (TRN). Unfortunately, our global understanding of the TRN in this emerging opportunistic pathogen is limited. Here, we apply independent component analysis, an unsupervised machine learning method, to a compendium of 139 RNA-seq data sets of three multidrug-resistant A. baumannii international clonal complex I strains (AB5075, AYE, and AB0057). This analysis allows us to define 49 independently modulated gene sets, which we call iModulons. Analysis of the identified A. baumannii iModulons reveals validating parallels to previously defined biological operons/regulons and provides a framework for defining unknown regulons. By utilizing the iModulons, we uncover potential mechanisms for a RpoS-independent general stress response, define global stress-virulence trade-offs, and identify conditions that may induce plasmid-borne multidrug resistance. The iModulons provide a model of the TRN that emphasizes the importance of transcriptional regulation of virulence phenotypes in A. baumannii. Furthermore, they suggest the possibility of future interventions to guide gene expression toward diminished pathogenic potential.IMPORTANCEThe rise in hospital outbreaks of multidrug-resistant Acinetobacter baumannii infections underscores the urgent need for alternatives to traditional broad-spectrum antibiotic therapies. The success of A. baumannii as a significant nosocomial pathogen is largely attributed to its ability to resist antibiotics and survive environmental stressors. However, there is limited literature available on the global, complex regulatory circuitry that shapes these phenotypes. Computational tools that can assist in the elucidation of A. baumanniis transcriptional regulatory network architecture can provide much-needed context for a comprehensive understanding of pathogenesis and virulence, as well as for the development of targeted therapies that modulate these pathways
A disruptive ethnography of Tanzanian-Indians
This paper is a disruptive ethnography of Indians in Tanzania (Tanzanian-Indians). It uses narratives of individuals to challenge the popular ethnographic categories within which the individuals are usually subsumed. This paper analyses three critical questions concerning Category, Homeland and Community. Is the category Mhindi (‘Indian’ in Kiswahili) exhaustive as a cultural identity? What is the relationship of Tanzanian-Indians to their ‘homeland’ India? Does a community-based approach map on to the realities of everyday lives of Tanzanian-Indians? The focus will be on Zanzibar and Dar es Salaam. Both these neighbouring places have significant Indian presence and through ethnographic research using conversations, semi-structured interviews and the self-presentation of individuals through temples, mosques and clubs, we highlight the diversity of experience that lies behind the specific identity category of Mhindi