The equilibria that allow bacterial persistence in human hosts

Blaser, Martin J.; Kirschner, Denise E.

doi:10.1038/nature06198

Cited by 213 publications

(190 citation statements)

References 92 publications

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“…The first is dispersal of the etiologic agent, M. tuberculosis, populations of which were sustained at very low levels (N e ≅ 2) for ∼100 y by small numbers of human migrants who had intimate, sustained contact with susceptible hosts. In addition to sustained migration, variable transmission dynamics of TB may have cushioned small bacterial populations against extinction (35). The second process is expansion of the bacterial population, following a shift in host ecology favoring the pathogen.…”

Section: Discussionmentioning

confidence: 99%

Dispersal of Mycobacterium tuberculosis via the Canadian fur trade

Pepperell

Granka

Alexander

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Patterns of gene flow can have marked effects on the evolution of populations. To better understand the migration dynamics of Mycobacterium tuberculosis , we studied genetic data from European M. tuberculosis lineages currently circulating in Aboriginal and French Canadian communities. A single M. tuberculosis lineage, characterized by the DS6 Quebec genomic deletion, is at highest frequency among Aboriginal populations in Ontario, Saskatchewan, and Alberta; this bacterial lineage is also dominant among tuberculosis (TB) cases in French Canadians resident in Quebec. Substantial contact between these human populations is limited to a specific historical era (1710–1870), during which individuals from these populations met to barter furs. Statistical analyses of extant M. tuberculosis minisatellite data are consistent with Quebec as a source population for M. tuberculosis gene flow into Aboriginal populations during the fur trade era. Historical and genetic analyses suggest that tiny M. tuberculosis populations persisted for ∼100 y among indigenous populations and subsequently expanded in the late 19th century after environmental changes favoring the pathogen. Our study suggests that spread of TB can occur by two asynchronous processes: ( i ) dispersal of M. tuberculosis by minimal numbers of human migrants, during which small pathogen populations are sustained by ongoing migration and slow disease dynamics, and ( ii ) expansion of the M. tuberculosis population facilitated by shifts in host ecology. If generalizable, these migration dynamics can help explain the low DNA sequence diversity observed among isolates of M. tuberculosis and the difficulties in global elimination of tuberculosis, as small, widely dispersed pathogen populations are difficult both to detect and to eradicate.

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Section: Discussionmentioning

confidence: 99%

Dispersal of Mycobacterium tuberculosis via the Canadian fur trade

Pepperell

Granka

Alexander

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…This process seems to be exceptional, however. Much more common are persisting microbes that the host cannot eliminate and which engage the host in an ongoing battle that damages tissues (14) and promotes malignancy. For example, squamous cell carcinomas follow the long-term inflammatory consequences of chronic osteomyelitis with sinus tract formation.…”

Section: Principles Of Microbial Oncogenesismentioning

confidence: 99%

“…Transmission within families occurs for many indigenous organisms (14) and can resemble inheritance patterns (55). Furthermore, whether a microbe is acquired from a family member (and so is preadapted to the next host) or from a genetically unrelated stranger could modify the risk of a disease that may present clinically decades later (46).…”

Section: Biological Considerationsmentioning

confidence: 99%

“…Investigations of what determines which heavy smokers do or do not develop lung cancer (and differential risk issues in other cancer settings) have focused on genetic differences among exposed individuals. It is becoming clear, however, that our indigenous microbes, the human microbiome, which consist of mutualistic or pathogenic, transient, or residential microbes (preponderantly bacteria) that normally inhabit the surfaces of human tissues (e.g., the lumen of the gastrointestinal tract), also may play a role in cancer risk because they are part of our metabolism and our very make-up (13)(14)(15)(16). Differences in the genes of the microbes we carry, encoding the microbial constituents expressed, and in the microbial products that interact with us (17) may affect differential susceptibility to disease (e.g., affecting hormone homeostasis and downstream cancers; refs.…”

mentioning

confidence: 99%

“…In a parallel fashion, varying exposures to microbial agents could modulate lung cancer risk among hosts of similar smoking status. Therefore, the "microbial" genotype of a host may be as relevant to disease risk as is the host's own "human" genotype (13)(14)(15)(16). Underscoring this issue, investigators have just discovered a previously unknown agent called the Merkel cell polyomavirus and evidence of its potential etiologic link with Merkel cell carcinoma, one of the most aggressive forms of skin cancer (20).…”

mentioning

confidence: 99%

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Understanding Microbe-Induced Cancers

Blaser

2008

Cancer Prevention Research

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Microbes are important causes of human cancers, and our estimation of their significance continues to grow as cancer biology is better dissected. A classification system is proposed that highlights common and proposed microbe-induced pathways toward oncogenesis, with an emphasis on types of targeted cells and host-microbial interactions. The central principles that underlie oncogenesis induced by the many diverse microbes and the major mechanisms involved are outlined. The phenomenon of microbe-induced cancers raises a number of important biological questions, the solving of which may inform other fields, including aging and degenerative disorders. Finally, our challenge for the future is to better understand the steps in microbe-induced cancers to optimize both prevention and therapy.

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Structural diversity in the Mycobacteria DUF3349 superfamily

et al. 2019

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A protein superfamily with a “Domain of Unknown Function,”, DUF3349 (PF11829), is present predominately in Mycobacterium and Rhodococcus bacterial species suggesting that these proteins may have a biological function unique to these bacteria. We previously reported the inaugural structure of a DUF3349 superfamily member, Mycobacterium tuberculosis Rv0543c. Here, we report the structures determined for three additional DUF3349 proteins: Mycobacterium smegmatis MSMEG_1063 and MSMEG_1066 and Mycobacterium abscessus MAB_3403c. Like Rv0543c, the NMR solution structure of MSMEG_1063 revealed a monomeric five α‐helix bundle with a similar overall topology. Conversely, the crystal structure of MSMEG_1066 revealed a five α‐helix protein with a strikingly different topology and a tetrameric quaternary structure that was confirmed by size exclusion chromatography. The NMR solution structure of a fourth member of the DUF3349 superfamily, MAB_3403c, with 18 residues missing at the N‐terminus, revealed a monomeric α‐helical protein with a folding topology similar to the three C‐terminal helices in the protomer of the MSMEG_1066 tetramer. These structures, together with a GREMLIN‐based bioinformatics analysis of the DUF3349 primary amino acid sequences, suggest two subfamilies within the DUF3349 family. The division of the DUF3349 into two distinct subfamilies would have been lost if structure solution had stopped with the first structure in the DUF3349 family, highlighting the insights generated by solving multiple structures within a protein superfamily. Future studies will determine if the structural diversity at the tertiary and quaternary levels in the DUF3349 protein superfamily have functional roles in Mycobacteria and Rhodococcus species with potential implications for structure‐based drug discovery.

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The equilibria that allow bacterial persistence in human hosts

Cited by 213 publications

References 92 publications

Dispersal of Mycobacterium tuberculosis via the Canadian fur trade

Dispersal of Mycobacterium tuberculosis via the Canadian fur trade

Understanding Microbe-Induced Cancers

Structural diversity in the Mycobacteria DUF3349 superfamily

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