Host-induced epidemic spread of the cholera bacterium

Merrell, D. Scott; Butler, Susan M.; Qadri, Firdausi; Dolganov, Nadia; Alam, Ahsfaqul; Cohen, Mitchell B.; Calderwood, Stephen B.; Schoolnik, Gary K.; Camilli, Andrew

doi:10.1038/nature00778

Cited by 484 publications

(394 citation statements)

References 17 publications

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“…14, 15 Our results show that the mobile working population (15-44 years of age) represented the greatest proportion of cases, strongly suggesting that the combination of a highly mobile infectious working population coming together in the overcrowded and unsanitary conditions found in markets significantly influenced the spread of cholera into the city through person to person transmission. [29][30][31] Our data are based on an estimated suburb population and we recognize that the estimates may not reflect the real figures during the epidemic. However we tried to take into account the natural average growth of the population in order to work with most realistic population estimates possible.…”

Section: Discussionmentioning

confidence: 99%

Descriptive spatial analysis of the cholera epidemic 2008–2009 in Harare, Zimbabwe: a secondary data analysis

Fernández

Mason

Gray

et al. 2011

Transactions of the Royal Society of Tropical Medicine and Hygi

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CitationDescriptive spatial analysis of the cholera epidemic [2008][2009] in Hopley. The identification of this spatial pattern in the spread, characterised by low risk in low density residential housing, and a higher risk in high density south west suburbs and Mbare, could be used to advocate for improving water and sanitation conditions and specific preparedness measures in the most affected areas.

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Section: Discussionmentioning

confidence: 99%

Descriptive spatial analysis of the cholera epidemic 2008–2009 in Harare, Zimbabwe: a secondary data analysis

Fernández

Mason

Gray

et al. 2011

Transactions of the Royal Society of Tropical Medicine and Hygi

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“…For instance, the first genome-wide transcriptomic studies of several important bacterial pathogens such as Vibrio cholerae (Merrell et al, 2002), Borrelia burgdorferi (Revel et al, 2002), Chlamydia trachomatis (Belland et al, 2003), C. pneumonia (Maurer et al, 2007) and S. Typhimurium (Eriksson et al, 2003) were performed with the help of microarrays and revealed gene expression patterns that suggested strategies used by these microbes to adapt to their host cells. Likewise, tiling arrays were applied to both in vitro and in vivo grown Listeria monocytogenes (Toledo-Arana et al, 2009) and used to identify sRNAs or novel virulence genes in streptococci (Kumar et al, 2010;Perez et al, 2009;Zheng et al, 2011).…”

Section: Transcriptomics: Then and Nowmentioning

confidence: 99%

Dual RNA-seq of pathogen and host

2012

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SummaryThe infection of a eukaryotic host cell by a bacterial pathogen is one of the most intimate examples of cross-kingdom interactions in biology. Infection processes are highly relevant from both a basic research as well as a clinical point of view. Sophisticated mechanisms have evolved in the pathogen to manipulate the host response and vice versa host cells have developed a wide range of anti-microbial defense strategies to combat bacterial invasion and clear infections.However, it is this diversity and complexity that makes infection research so challenging to technically address as common approaches have either been optimized for bacterial or eukaryotic organisms. Instead, methods are required that are able to deal with the often dramatic discrepancy between host and pathogen with respect to various cellular properties and processes. One class of cellular macromolecules that exemplify this host-pathogen heterogeneity is given by their transcriptomes: Bacterial transcripts differ from their eukaryotic counterparts in many aspects that involve both quantitative and qualitative traits. The entity of RNA transcripts present in a cell is of paramount interest as it reflects the cell's physiological state under the given condition. Genome-wide transcriptomic techniques such as RNA-seq have therefore been used for single-organism analyses for several years, but their applicability has been limited for infection studies.The present work describes the establishment of a novel transcriptomic approach for infection biology which we have termed "Dual RNA-seq". Using this technology, it was intended to shed light particularly on the contribution of non-protein-encoding transcripts to virulence, as these classes have mostly evaded previous infection studies due to the lack of suitable methods. The performance of Dual RNA-seq was evaluated in an in vitro infection model based on the important facultative intracellular pathogen Salmonella enterica serovar Typhimurium and different human cell lines. Dual RNA-seq was found to be capable of capturing all major bacterial and human transcript classes and proved reproducible. During the course of these experiments, a previously largely uncharacterized bacterial small non-coding RNA (sRNA), referred to as STnc440, was identified as one of the most strongly induced genes in intracellular Salmonella.Interestingly, while inhibition of STnc440 expression has been previously shown to cause a virulence defect in different animal models of Salmonellosis, the underlying molecular mechanisms have remained obscure. Here, classical genetics, transcriptomics and biochemical assays proposed a complex model of Salmonella gene expression control that is orchestrated by this sRNA. In particular, STnc440 was found to be involved in the regulation of multiple bacterial target mRNAs by direct base pair interaction with consequences for Salmonella virulence and

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“…These genes are upregulated in response to physical and chemical signals that are encountered in the host environment. Other signals indicate that the bacterium has exited the host (Merrell et al 2002). Experiments with many pathogens involved in a wide variety of infections have shown that these infectionrelevant signals modulate the supercoiling of bacterial DNA, providing a background regulatory influence upon which the dedicated gene regulatory proteins operate.…”

Section: Dna Supercoiling Bacterial Evolution and Pathogenesismentioning

confidence: 99%

DNA supercoiling is a fundamental regulatory principle in the control of bacterial gene expression

Dorman

2016

Biophys Rev

107

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Although it has become routine to consider DNA in terms of its role as a carrier of genetic information, it is also an important contributor to the control of gene expression. This regulatory principle arises from its structural properties. DNA is maintained in an underwound state in most bacterial cells and this has important implications both for DNA storage in the nucleoid and for the expression of genetic information. Underwinding of the DNA through reduction in its linking number potentially imparts energy to the duplex that is available to drive DNA transactions, such as transcription, replication and recombination. The topological state of DNA also influences its affinity for some DNA binding proteins, especially in DNA sequences that have a high A + T base content. The underwinding of DNA by the ATP-dependent topoisomerase DNA gyrase creates a continuum between metabolic flux, DNA topology and gene expression that underpins the global response of the genome to changes in the intracellular and external environments. These connections describe a fundamental and generalised mechanism affecting global gene expression that underlies the specific control of transcription operating through conventional transcription factors. This mechanism also provides a basal level of control for genes acquired by horizontal DNA transfer, assisting microbial evolution, including the evolution of pathogenic bacteria.

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Host-induced epidemic spread of the cholera bacterium

Cited by 484 publications

References 17 publications

Descriptive spatial analysis of the cholera epidemic 2008–2009 in Harare, Zimbabwe: a secondary data analysis

Descriptive spatial analysis of the cholera epidemic 2008–2009 in Harare, Zimbabwe: a secondary data analysis

Dual RNA-seq of pathogen and host

DNA supercoiling is a fundamental regulatory principle in the control of bacterial gene expression

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