Engineering of obligate intracellular bacteria: progress, challenges and paradigms

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Abstract

In this Review, Pedra and colleagues describe the advances and challenges in the genetic engineering of obligate intracellular bacteria, and highlight examples of how the use of genetically manipulated pathogens has improved our understanding of microbial pathogenesis and host–pathogen interactions.

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Bacterial iron homeostasis.

Simon C. Andrews, Andrea Robinson, Francisco Rodríguez-Quiñones (2003)

Iron is essential to virtually all organisms, but poses problems of toxicity and poor solubility. Bacteria have evolved various mechanisms to counter the problems imposed by their iron dependence, allowing them to achieve effective iron homeostasis under a range of iron regimes. Highly efficient iron acquisition systems are used to scavenge iron from the environment under iron-restricted conditions. In many cases, this involves the secretion and internalisation of extracellular ferric chelators called siderophores. Ferrous iron can also be directly imported by the G protein-like transporter, FeoB. For pathogens, host-iron complexes (transferrin, lactoferrin, haem, haemoglobin) are directly used as iron sources. Bacterial iron storage proteins (ferritin, bacterioferritin) provide intracellular iron reserves for use when external supplies are restricted, and iron detoxification proteins (Dps) are employed to protect the chromosome from iron-induced free radical damage. There is evidence that bacteria control their iron requirements in response to iron availability by down-regulating the expression of iron proteins during iron-restricted growth. And finally, the expression of the iron homeostatic machinery is subject to iron-dependent global control ensuring that iron acquisition, storage and consumption are geared to iron availability and that intracellular levels of free iron do not reach toxic levels.

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Chlamydia cell biology and pathogenesis.

Cherilyn A. Elwell, Kathleen M Mirrashidi, Joanne N. Engel (2016)

Chlamydia spp. are important causes of human disease for which no effective vaccine exists. These obligate intracellular pathogens replicate in a specialized membrane compartment and use a large arsenal of secreted effectors to survive in the hostile intracellular environment of the host. In this Review, we summarize the progress in decoding the interactions between Chlamydia spp. and their hosts that has been made possible by recent technological advances in chlamydial proteomics and genetics. The field is now poised to decipher the molecular mechanisms that underlie the intimate interactions between Chlamydia spp. and their hosts, which will open up many exciting avenues of research for these medically important pathogens.

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Anaplasma phagocytophilum—a widespread multi-host pathogen with highly adaptive strategies

Snorre Stuen, Erik Granquist, Cornelia Silaghi (2013)

The bacterium Anaplasma phagocytophilum has for decades been known to cause the disease tick-borne fever (TBF) in domestic ruminants in Ixodes ricinus-infested areas in northern Europe. In recent years, the bacterium has been found associated with Ixodes-tick species more or less worldwide on the northern hemisphere. A. phagocytophilum has a broad host range and may cause severe disease in several mammalian species, including humans. However, the clinical symptoms vary from subclinical to fatal conditions, and considerable underreporting of clinical incidents is suspected in both human and veterinary medicine. Several variants of A. phagocytophilum have been genetically characterized. Identification and stratification into phylogenetic subfamilies has been based on cell culturing, experimental infections, PCR, and sequencing techniques. However, few genome sequences have been completed so far, thus observations on biological, ecological, and pathological differences between genotypes of the bacterium, have yet to be elucidated by molecular and experimental infection studies. The natural transmission cycles of various A. phagocytophilum variants, the involvement of their respective hosts and vectors involved, in particular the zoonotic potential, have to be unraveled. A. phagocytophilum is able to persist between seasons of tick activity in several mammalian species and movement of hosts and infected ticks on migrating animals or birds may spread the bacterium. In the present review, we focus on the ecology and epidemiology of A. phagocytophilum, especially the role of wildlife in contribution to the spread and sustainability of the infection in domestic livestock and humans.

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Journal

Title: Nature Reviews Microbiology

Abbreviated Title: Nat Rev Micro

Publisher: Springer Nature

ISSN (Print): 1740-1526

ISSN (Electronic): 1740-1534

Publication date Created: June 19 2017

Publication date (Print): June 19 2017

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DOI: 10.1038/nrmicro.2017.59

PMC ID: 5557331

PubMed ID: 28626230

SO-VID: ad9d0270-c6c6-4c73-828a-ebed06693ec5

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Engineering of obligate intracellular bacteria: progress, challenges and paradigms

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Most cited references 94

Bacterial iron homeostasis.

Chlamydia cell biology and pathogenesis.

Anaplasma phagocytophilum—a widespread multi-host pathogen with highly adaptive strategies

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