Microbial genomics: tropical treasure?

A Brazilian consortium has unveiled the genomic DNA sequence of the purple-pigmented bacterium Chromobacterium violaceum, a dominant component of the tropical soil microbiota. The sequence provides insight into the abundant potential of this organism for biotechnological and pharmaceutical applications.     

Microbial genomics: rhetoric or reality?

The availability of complete genome sequences of many bacterial species is facilitating numerous computational approaches for understanding bacterial genomes. One of the major incentives behind the genome sequencing of many pathogenic bacteria is the desire to better understand their diversity and to develop new approaches for controlling human diseases caused by these microorganisms. This task has become even more urgent with the rapid evolution of antibiotic resistance among many bacterial pathogens. Novel drug targets are required in order to design new antimicrobials against antibiotic-resistant pathogens. The complete genome sequences of an ever increasing number of pathogenic microbes constitute an invaluable resource and provide lead information on potential drug targets. This review focuses on in silico analyses of microbial genomes, their host-specific adaptations, with specific reference to genome architecture, design, evolution, and trends in computational identification of microbial drug targets. These trends underscore the utility of genomic data for systematic in silico drug target identification in the post-genomic era.     

Microbial invasion: a covert activity?

In contrast to nonpathogenic microorganisms that exist happily in biofilms on various organic and inorganic surfaces, many pathogenic microbes have the additional ability to invade host tissues by inducing their own endocytosis and transport across normally protective barriers. This phenomenon, designated "parasite-directed endocytosis," has been observed with a variety of surfaces (intestinal, genital, nasopharyngeal, and tracheal epithelium) as well as in endothelial cells. The mechanisms involved in invasion may involve a single factor as described for some species of Yersinia, or may require multiple factors as observed in Shigellae. For the majority of pathogens, the molecular mechanisms of invasion are not well understood (e.g., Neisseria gonorrhoeae). Because parasite-directed endocytosis is reminiscent of receptor-mediated endocytosis, it is quite possible that some pathogens engage in biologic mimicry by producing a molecule that resembles a natural host ligand, for which there is a host cell receptor. Such a masquerade may allow some microbes to enter the host's inner sanctum covertly in a manner analogous to the Trojan horse, rather than overtly by destroying the mucosa and entering host tissues directly. Whereas this hypothesis is speculative at present, bacteria that produce molecules resembling insulin, calmodulin, and chorionic gonadotropin have been described.     

Microbial endemism: does phosphorus limitation enhance speciation?

There is increasing evidence for the existence of unique ecosystems that are dominated by locally adapted microbiota which harbour distinct lineages and biological capabilities, much like the macrobiota of Darwin's Galapagos Islands. As a primary example of such a system, we highlight key discoveries from the Cuatro Ciénegas basin in Mexico. We argue that high microbial endemism requires a combination of geographical isolation, long-term continuity and mechanisms for reducing the intensity of horizontal gene transfer (HGT). We also propose that strong phosphorus limitation has an important role in microbial diversification by reducing the intensity of HGT.     

Microbial metal-ion reduction and Mars: extraterrestrial expectations?

Dissimilatory metal-ion-reducing bacteria (DMRB) can couple the reduction of a variety of different metal ions to cellular respiration and growth. The excitement of this metabolic group lies not only in the elucidation of a new type of metabolism, but also in the potential use of these abilities for the removal of toxic organics, and in their ability to reduce (and thus, detoxify) other toxic metals, such as U(VI) and Cr(VI). This review focuses on recent advances in the study of DMRB, including the use of external electron shuttles to enhance rates of metal reduction; genome sequencing and consequent genomic and proteomic analyses; new imaging approaches for high resolution analysis of both cells and chemical components; the demonstration of fractionation of stable isotopes of iron during iron reduction; and the elucidation of the types and patterns of secondary mineral formation during metal reduction. One of the secondary minerals is magnetite, the subject of intense controversy regarding the possibility of evidence for life from the Martian meteorite ALH84001. This review thus ends with a short consideration of the evidence for magnetic 'proof' of the existence of past life on Mars.     

Microbial βγ-crystallins

βγ-Crystallins have emerged as a superfamily of structurally homologous proteins with representatives across the domains of life. A major portion of this superfamily is constituted by members from microorganisms. This superfamily has also been recognized as a novel group of Ca²⁺-binding proteins with huge diversity. The βγ domain shows variable properties in Ca²⁺ binding, stability and association with other domains. The various members present a series of evolutionary adaptations culminating in great diversity in properties and functions. Most of the predicted βγ-crystallins are yet to be characterized experimentally. In this review, we outline the distinctive features of microbial βγ-crystallins and their position in the βγ-crystallin superfamily.     

Microbial α-mannosidases

Microbial α-mannosidases are used in the analysis of glycopeptides and the developmental regulation of lysosomal enzymes. This survey presents comparison of properties of this high molecular weight, oligomeric protein from a number of microbial sources.     

Microbial nanowires: type IV pili or cytochrome filaments?

A dynamic field of study has emerged involving long-range electron transport by extracellular filaments in anaerobic bacteria, with Geobacter sulfurreducens being used as a model system. The interest in this topic stems from the potential uses of such systems in bioremediation, energy generation, and new bio-based nanotechnology for electronic devices. These conductive extracellular filaments were originally thought, based upon low-resolution observations of dried samples, to be type IV pili (T4P). However, the recently published atomic structure for the T4P from G. sulfurreducens, obtained by cryo-electron microscopy (cryo-EM), is incompatible with the numerous models that have been put forward for electron conduction. As with all high-resolution structures of T4P, the G. sulfurreducens T4P structure shows a partial melting of the α-helix that substantially impacts the aromatic residue positions such that they are incompatible with conductivity. Furthermore, new work using high-resolution cryo-EM shows that conductive filaments thought to be T4P are actually polymerized cytochromes, with stacked heme groups forming a continuous conductive wire, or extracellular DNA. Recent atomic structures of three different cytochrome filaments from G. sulfurreducens suggest that such polymers evolved independently on multiple occasions. The expectation is that such polymerized cytochromes may be found emanating from other anaerobic organisms.     

Microbial cholesterol oxidases: bioconversion enzymes or signal proteins?

Cholesterol oxidases (3beta-hydroxysterol oxidases; EC 1.1.3.6), serve as catalysts for the initial step in the degradation of cholesterol, and probably other natural sterols, that are used as carbon sources for growth of different bacteria. Because of their suitability for attacking cholesterol they have been widely used for the quantification of cholesterol in clinical and food specimens. Cholesterol oxidase has also found application as a probe for membrane structure, as an insecticide, and has been implicated in bacterial pathogenesis. Recently, we have found that a Streptomyces cholesterol oxidase is required for the biosynthesis of the antifungal polyene pimaricin, apparently acting as an antifungal sensor. Here we describe our current understanding of these fascinating enzymes.