The changing concept of organism in microbiology.
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Bacteria↗
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Metazoan and microbial models of Niemann-Pick Type C disease.
Niemann-Pick Type C (NP-C) disease compellingly provides insight into lipid transport and the association of this process with severe neuronal dysfunction. The two genes that define this syndrome, NPC1 and NPC2, are conserved throughout much of eukaryotic evolution, to the extent that the yeast and mammalian NPC1 genes are functionally interchangeable. We present here an evolutionary perspective of the genes defective in NP-C disease. We will describe how conservation of sequences and their biological roles in a variety of microbial and metazoan model systems may act as roadmaps to understanding this syndrome in humans.
Amino Acid Sequence↗
Sepsis and evolution of the innate immune response.
OBJECTIVE: To review the role of the Toll-like receptors (TLR) as the principal sensors used by the innate immune system in the context of the pathologic processes underlying sepsis and septic shock. DATA SOURCES: Literature review. DATA SUMMARY: Through the Toll-like receptors, macrophages and other defensive cells "see" endotoxin (TLR4), peptidoglycan (TLR2), and bacterial DNA (TLR9). Representatives of the family predated the divergence of plants and animals and, at that time, had already acquired a defensive function. The strengths and liabilities of the innate immune system, which defends against infection and which also may cause shock and death, are rooted in its ancient origins. In the current era of shock research, the nature of the signals that Toll-like receptors transduce and the effects of genetic variation on microbial sensing are two major challenges.
Animals↗
The prevalence and evolution of sex in microorganisms.
The origin of sex and how sex is maintained are among the biggest puzzles in biology. Most investigations into this problem have focused on complex eukaryotes like animals and plants. This mini-review summarizes recent progress in our understanding of the evolution of sex, highlighting results from studies of experimental and natural populations of microorganisms. Increasing evidence indicates that sexual reproduction in natural populations of viruses, bacteria, and eukaryotic microbes is much more prevalent than previously thought. In addition, investigations using experimental microbial populations are providing important parameters relevant to our understanding of the origin and maintenance of sex. It is argued that microbes are excellent model organisms to explore the mechanisms responsible for the evolution of sex.
Animals↗
New findings on evolution of metal homeostasis genes: evidence from comparative genome analysis of bacteria and archaea.
In order to examine the natural history of metal homeostasis genes in prokaryotes, open reading frames with homology to characterized P(IB)-type ATPases from the genomes of 188 bacteria and 22 archaea were investigated. Major findings were as follows. First, a high diversity in N-terminal metal binding motifs was observed. These motifs were distributed throughout bacterial and archaeal lineages, suggesting multiple loss and acquisition events. Second, the CopA locus separated into two distinct phylogenetic clusters, CopA1, which contained ATPases with documented Cu(I) influx activity, and CopA2, which contained both efflux and influx transporters and spanned the entire diversity of the bacterial domain, suggesting that CopA2 is the ancestral locus. Finally, phylogentic incongruences between 16S rRNA and P(IB)-type ATPase gene trees identified at least 14 instances of lateral gene transfer (LGT) that had occurred among diverse microbes. Results from bootstrapped supported nodes indicated that (i) a majority of the transfers occurred among proteobacteria, most likely due to the phylogenetic relatedness of these organisms, and (ii) gram-positive bacteria with low moles percent G+C were often involved in instances of LGT. These results, together with our earlier work on the occurrence of LGT in subsurface bacteria (J. M. Coombs and T. Barkay, Appl. Environ. Microbiol. 70:1698-1707, 2004), indicate that LGT has had a minor role in the evolution of P(IB)-type ATPases, unlike other genes that specify survival in metal-stressed environments. This study demonstrates how examination of a specific locus across microbial genomes can contribute to the understanding of phenotypes that are critical to the interactions of microbes with their environment.
Adenosine Triphosphatases↗
Genomic functional annotation using co-evolution profiles of gene clusters.
BACKGROUND: The current speed of sequencing already exceeds the capability of annotation, creating a potential bottleneck. A large proportion of the genes in microbial genomes remains uncharacterized. Here we propose a new method for functional annotation using the conservation patterns of gene clusters. If several gene clusters show the same coevolution pattern across different genomes it is reasonable to infer they are functionally related. The gene cluster phylogenetic profile integrates chromosomal proximity information and phylogenetic profile information and allows us to infer functional dependences between the gene clusters even at great distance on the chromosome. RESULTS: As a proof of concept, we applied our method to the genome of Escherichia coli K12 strain. Our method establishes functional relationships among 176 gene clusters, comprising 738 E. coli genes. The accuracy of pair phylogenetic profiles was compared with the single-gene phylogenetic profile and was shown to be higher. As a result, we are able to suggest functional roles for several previously unknown genes or unknown genomic regions in E. coli. We also examined the robustness of coevolution signals across a larger set of genomes and suggest a possible upper limit of accuracy for the phylogenetic profile methods. CONCLUSIONS: The higher-order phylogenetic profiles, such as the gene-pair phylogenetic profiles, can detect functional dependences that are missed by using conventional single-gene phylogenetic profile or the chromosomal proximity method only. We show that the gene-pair phylogenetic profile is more accurate than the single-gene phylogenetic profiles.
Alleles↗
Non-divergence theory of evolution: sequence comparison of some proteins from snakes and bacteria.
A "non-divergence theory" is proposed for the mechanism of evolution. The theory is based on the observation that comparison of the amino acid sequences of related proteins in various organisms gives inconsistent results from one type of protein to another, and on the occurrence of significant gene transfer among living organisms. Special attention is focused on the sequence comparisons of short- and long-chain neurotoxins and phospholipases A2 from the venoms of proteroglyphous snakes and those of microbial ferredoxins, rubredoxins, and flavodoxins.
Amino Acid Sequence↗
The evolution and maintenance of virulence in Staphylococcus aureus: a role for host-to-host transmission?
Despite progress in our understanding of infectious disease biology and prevention, the conditions that select for the establishment and maintenance of microbial virulence remain enigmatic. To address this aspect of pathogen biology, we focus on two members of the Staphylococcus genus - Staphylococcus aureus and Staphylococcus epidermidis - and consider why S. aureus has evolved to become more virulent than S. epidermidis. Several hypotheses to explain this phenomenon are discussed and a mathematical model is used to argue that a complex transmission pathway is the key factor in explaining the evolution and maintenance of virulence in S. aureus. In the case of S. epidermidis, where skin contact affords easier transmission between hosts, high levels of virulence do not offer an advantage to this pathogen.
Adaptation, Biological↗
Dispelling the myths--biocatalysis in industrial synthesis.
Biocatalysis has emerged as an important tool in the industrial synthesis of bulk chemicals, pharmaceutical and agrochemical intermediates, active pharmaceuticals, and food ingredients. However, the number and diversity of the applications are modest, perhaps in part because of perceived or real limitations of biocatalysts, such as limited enzyme availability, substrate scope, and operational stability. Recent scientific breakthroughs in genomics, directed enzyme evolution, and the exploitation of biodiversity should help to overcome these limitations. As a result, we expect many new industrial applications of biocatalysis to be realized, from single-step enzymatic conversions to customized multistep microbial synthesis by means of metabolic pathway engineering.
Biotechnology↗
Host-microbe interactions: shaping the evolution of the plant immune response.
The evolution of the plant immune response has culminated in a highly effective defense system that is able to resist potential attack by microbial pathogens. The primary immune response is referred to as PAMP-triggered immunity (PTI) and has evolved to recognize common features of microbial pathogens. In the coevolution of host-microbe interactions, pathogens acquired the ability to deliver effector proteins to the plant cell to suppress PTI, allowing pathogen growth and disease. In response to the delivery of pathogen effector proteins, plants acquired surveillance proteins (R proteins) to either directly or indirectly monitor the presence of the pathogen effector proteins. In this review, taking an evolutionary perspective, we highlight important discoveries over the last decade about the plant immune response.
Bacteria↗
Prokaryotic lifestyles in deep sea habitats.
Gradients of physicochemical factors influence the growth and survival of life in deep-sea environments. Insights into the characteristics of deep marine prokaryotes has greatly benefited from recent progress in whole genome and metagenome sequence analyses. Here we review the current state-of-the-art of deep-sea microbial genomics. Ongoing and future genome-enabled studies will allow for a better understanding of deep-sea evolution, physiology, biochemistry, community structure and nutrient cycling.
Genome↗
Organic carbon concentration profiles in recent cave sediments: records of agricultural pollution or diagenesis?
Recent (<7 years old) cave sediments in Speedwell Cavern, Derbyshire, show an approximately exponential decay of organic carbon with depth. This phenomenon was thought to be due to one of two causes: (i) changing agricultural practice within the catchment feeding the cave, especially the increased use of sewage sludge and animal slurry as fertilizer; (ii) a relatively constant organic carbon concentration over time in the input sediment, with subsequent carbon mineralization during diagenesis. Carbon isotope composition of the organic material and the evolution of H/C ratio with depth indicate that the latter hypothesis is correct and that the profiles result from microbial diagenesis, not increased organic carbon inputs. By comparison with sediment of known (7 years) age, temporal decay constants for organic matter can be derived; these lie between rates previously determined for organic matter decomposition in marine sediments and soils. The H/C ratio of organic matter can be modelled as a function of time and proceeds in a similar fashion to soil organic material.
Journal Article↗
Molecular analysis of ancient microbial infections.
The detection of ancient microbial DNA offers a new approach for the study of infectious diseases, their occurrence, frequency and host-pathogen interaction in historic times and populations. Moreover, data obtained from skeletal and mummified tissue may represent an important completion of contemporary phylogenetic analyses of pathogens. In the last few years, a variety of bacterial, protozoal and viral infections have been detected in ancient tissue samples by amplification and characterization of specific DNA fragments. This holds particularly true for the identification of the Mycobacterium tuberculosis complex, which seems to be more robust than other microbes due to its waxy, hydrophobic and lipid-rich cell wall. These observations provided useful information about the occurrence, but also the frequency of tuberculosis in former populations. Moreover, these studies suggest new evolutionary models and indicate the route of transmission between human and animals. Until now, other pathogens, such as Mycobacterium leprae, Yersinia pestis, Plasmodium falciparum and others, have occasionally been identified - mostly in single case studies or small sample sizes - as well, although much less information is available on these pathogens in ancient settings. The main reason therefore seems to be the degradation and modification of ancient DNA by progressive oxidative damage. Furthermore, the constant risk of contamination by recent DNA forces to take time and cost effective measures and renders the analysis of ancient microbes difficult. Nevertheless, the study of microbial ancient DNA significantly contributes to the understanding of transmission and spread of infectious diseases, and potentially to the evolution and phylogenetic pathways of pathogens.
Animals↗
Primary structure of microbial transglutaminase from Streptoverticillium sp. strain s-8112.
The complete amino acid sequence of transglutaminase (EC 2.3.2.13) (TGase), which is produced by a microorganism, Streptoverticillium sp. strain s-8112, and catalyzes the acyl transfer reaction between gamma-carboxyamide groups of glutamine residues in proteins and various primary amines, has been established by a combination of fast atom bombardment mass spectrometry and standard Edman degradation of peptide fragments produced by treatment of the TGase with various proteolytic enzymes and purified by a reversed-phase high performance liquid chromatography. The TGase consists of 331 amino acid residues with a chemical molecular weight of 37,863, in agreement with the observed molecular weight (37,869.2 +/- 8.8) determined from its electrospray ionization mass spectrum. The sequence of the enzyme is very different from those of mammalian TGases represented by guinea pig liver enzyme. The enzyme contains a sole Cys residue, which is essential for its catalytic activity. Hydropathy analysis indicated that the secondary structure of the region around the active site Cys residue is similar to those of mammalian TGases. These results suggest that this microbial protein evolved by a different pathway from that of mammalian TGases and acquired acyl transfer activity during the evolutional process.
Amino Acid Sequence↗
Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection.
The seminal work of Le Douarin and colleagues (Ohki et al. 1987; Ohki et al. 1988; Salaun et al. 1990; Coutinho et al. 1993) first demonstrated that peripheral tissue-specific tolerance is centrally established in the thymus, by epithelial stromal cells (TEC). Subsequent experiments have shown that TEC-tolerance is dominant and mediated by CD4 regulatory T cells (Treg) that are generated intrathymically by recognition of antigens expressed on TECs (Modigliani et al. 1995; Modigliani et al. 1996a). From these and other observations, in 1996 Modigliani and colleagues derived a general model for the establishment and maintenance of natural tolerance (MM96) (Modigliani et al. 1996b), with two central propositions: (1) T cell receptor (TCR)-dependent sorting of emergent repertoires generates TEC-specific Treg displaying the highest TCR self-affinities below deletion thresholds, thus isolating repertoires undergoing positive and negative selection; (2) Treg are intrathymically committed (and activated) for a unique differentiative pathway with regulatory effector functions. The model explained the embryonic/perinatal time window of natural tolerance acquisition, by developmental programs determining (1) TCR multireactivity, (2) the cellular composition in the thymic stroma (relative abundance of epithelial vs hemopoietic cells), and (3) the dynamics of peripheral lymphocyte pools, built by accumulation of recent thymic emigrants (RTE) that remain recruitable to regulatory functions. We discuss here the MM96 in the light of recent results demonstrating the promiscuous expression of tissue-specific antigens by medullary TECs (Derbinski et al. 2001; Anderson et al. 2002; Gotter et al. 2004) and indicating that Treg represent a unique differentiative pathway (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003), which is adopted by CD4 T cells with high avidity for TEC-antigens (Bensinger et al. 2001; Jordan et al. 2001; Apostolou et al. 2002). In the likelihood that autoimmune diseases (AID) result from Treg deficits, some of which might have a thymic origin, we also speculate on therapeutic strategies aiming at selectively stimulating their de novo production or peripheral function, within recent findings on Treg responses to inflammation (Caramalho et al. 2003; Lopes-Carvalho et al., submitted, Caramalho et al., submitted). In short, the MM96 argued that natural tolerance is dominant, established and maintained by the activity of Treg, which are selected upon high-affinity recognition of self-ligands on TECs, and committed intrathymically to a unique differentiative pathway geared to anti-inflammatory and antiproliferative effector functions. By postulating the intrathymic deletion of self-reactivities on hemopoietic stromal cells (THC), together with the inability of peripheral resident lymphocytes to engage in the regulatory pathway, the MM96 simultaneously explained the maintenance of responsiveness to non-self in a context of suppression mediating dominant self-tolerance. The major difficulty of the MM96 is related to the apparent tissue specificity of Treg repertoires generated intrathymically. This difficulty has now been principally solved by the work of Hanahan, Kyewski and others (Jolicoeur et al. 1994; Derbinski et al. 2001; Anderson et al. 2002; Gotter et al. 2004), demonstrating the selective expression of a variety of tissue-specific antigens by TECs, in topological patterns that are compatible with the MM96, but difficult to conciliate with recessive tolerance models (Kappler et al. 1987; Kisielow et al. 1988). While the developmentally regulated multireactivity of TCR repertoires (Gavin and Bevan 1995), as well as the peripheral recruitment of Treg among RTE (Modigliani et al. 1996a) might add to this process, it would seem that the establishment of tissue-specific tolerance essentially stems from the "promiscuous expression of tissue antigens" by TEC. The findings of AID resulting from natural mutations (reviewed in Pitkanen and Peterson 2003) or the targeted inactivation (Anderson et al. 2002; Ramsey et al. 2002) of the AIRE transcription factor that regulates promiscuous gene expression on TECs support this conclusion. The observations on the correlation of natural or forced expression of the Foxp3 transcription factor in CD4 T cells with Treg phenotype and function (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003) provided support for the MM96 contention that Treg represent a unique differentiative pathway that is naturally established inside the thymus. Furthermore, Caton and colleagues (Jordan et al. 2001), as well as several other groups (Bensinger et al. 2001; Apostolou et al. 2002), have provided direct evidence for our postulate that Treg are selected among differentiating CD4 T cells with high affinity for ligands expressed on TECs (Modigliani et al. 1996b). Finally, the demonstration by Caramalho et al. that Treg express innate immunity receptors (Caramalho et al. 2003) and respond to pro-inflammatory signals and products of inflammation (Caramalho et al., submitted) brought about a new understanding on the peripheral regulation of Treg function. Together with the observation that Treg also respond to ongoing activities of "naïve/effector" T cells--possibly through the IL-2 produced in these conditions--these findings explain the participation of Treg in all immune responses (Onizuka et al. 1999; Shimizu et al. 1999; Annacker et al. 2001; Curotto de Lafaille et al. 2001; Almeida et al. 2002; Shevach 2002; Bach and Francois Bach 2003; Wood and Sakaguchi 2003; Mittrucker and Kaufmann 2004; Sakaguchi 2004), beyond their fundamental role in ensuring self-tolerance (e.g., Modigliani et al. 1996a; Shevach 2000; Hori et al. 2003; Sakaguchi 2004; Thompson and Powrie 2004). Thus, anti-inflammatory and anti-proliferative Treg are amplified by signals that promote or mediate inflammation and proliferation, accounting for the quality control of responses (Coutinho et al. 2001). In turn, such natural regulation of Treg by immune responses to non-self may well explain the alarming epidemiology of allergic and AID in wealthy societies (Wills-Karp et al. 2001; Bach 2002; Yazdanbakhsh et al. 2002), where a variety of childhood infections have become rare or absent. Thus, it is plausible that Treg were evolutionarily set by a given density of infectious agents in the environment. With hindsight, it is not too surprising that natural Treg performance falls once hygiene, vaccination, and antibiotics suddenly (i.e., 100 years) plunged infectious density to below some critical physiological threshold. As the immune system is not adapted to modern clean conditions of postnatal development, clinical immunologists must now deal with frequent Treg deficiencies (allergies and AID) for which they have no curative or rational treatments. It is essential, therefore, that basic immunologists concentrate on strategies to selectively stimulate the production, survival, and activity of this set of lymphocytes that is instrumental in preventing immune pathology. We have argued that the culprit of this inability of basic research to solve major clinical problems has been the self-righteousness of recessive tolerance champions, from Ehrlich to some of our contemporaries. It is ironical, however, that none of us--including the heretic opponents of horror autotoxicus--had understood that self-tolerance, or its robustness at least, is in part determined by the frequency and intensity of the responses to non-self. In the evolution of ideas on immunological tolerance, the time might be ripe for some kinds of synthesis. First, conventional theory reduced self-tolerance to negative selection and microbial defense to positive selection, while the MM96 solution was the precise opposite: positive selection of autoreactivities for self-tolerance (Treg) and negative selection (of Treg) for ridding responses. In contrast, it would now appear that positive and negative selection of autoreactive T cells are both necessary to establish either self-tolerance or competence to eliminate microbes, two processes that actually reinforce each other in the maintenance of self-integrity. Second, V-region recognition has generally been held responsible for specific discrimination between what should be either tolerated or eliminated from the organism. In contrast again, it would now seem that both processes of self-tolerance and microbial defense (self/non-self discrimination) also operate on the basis of evolutionarily ancient, germ-line-encoded innate, nonspecific receptors (Medzhitov and Janeway 2000) capable of a coarse level of self/non-self discrimination (Coutinho 1975). It could thus be interesting to revisit notions of cooperativity between V-regions and such mitogen receptors, both in single cell functions (Coutinho et al. 1974) and in the system's evolution (Coutinho 1975, 1980) as well. After all, major transitions in evolution were cooperative (Maynard-Smith and Szathmary 1995).
Animals↗
Collateral sensitivity-harnessing microbial vulnerabilities as a solution to antimicrobial resistance.
Bacteria exhibit an evolutionary trade-off through their development of collateral sensitivity (CS) which allows them to resist one antibiotic while becoming more vulnerable to another. This vulnerability offers a compelling therapeutic opportunity by selecting against resistant isolates. Laboratory evolution studies, genome sequencing, deep mutagenesis and use of artificial intelligence and machine learning can design the bespoke strategy against multi-drug-resistant bacteria. This review discusses about recent studies that are rationally designed to harness this evolutionary trade-off for the development of alternative antimicrobial strategies. The translational barriers to the clinical implementation of CS are addressed and evidence-based design principles for optimization of CS-guided therapy are discussed.
Bacteria↗
[Alteration of cartilage by microbial agents and granulocytes].
Severe polyarthritis was induced in 42 SPF piglets by subcutaneous and intraarticular infection in one joint of the bacterium Erysipelothrix rhusiopathiae (Serotype B, strain T 28), which in its chronic stage morphologically resembles human c.P. The light and electron microscopic examination of the articular cartilage and synovial membrane reveals a parallel evolution of hyaline cartilage degeneration, and activation and proliferation of synovial lining cells. The initial cartilage alteration with demasking of collagen fibrils and focal degeneration of chondrocytes in the erysipelas model is caused by direct action of the microbial agent, fibrin and few granulocytes Erysipelothrix bacteria and neutrophilic granulocytes are able to invade the superficial and intermediate cartilage layers. This model is not considered a suppurative infectious arthritis. In chronic villous erysipelas polyarthritis, which develops without the presence of neutrophils in the cartilage, the invasively growing synovial pannus dominates, which deeply destroys the pre-damaged cartilage, resulting in macroscopic focal or wide-spread cartilage erosion. We consider the poorly vascularized cartilage and the particular fibrosis suitable sites for the extremely long (up to three years) persistence of this microbial agent. The persistence of the agent is considered necessary for the persisting immunological reactions and the perpetuation of erysipelas polyarthritis. With longer duration (1-3 years) of experimental erysipelas polyarthritis the number of bacteriologically positive arthritic joint decreases. Microscopically, the causative bacteria may only sporadically identified.
Animals↗
A Comprehensive Review on the Biosynthesis of Tropane Alkaloids.
Tropane alkaloids (TA) constitute a class of plant specialized metabolites with important pharmaceutical applications, including the anticholinergic agents hyoscyamine and scopolamine and the local anesthetic cocaine. Over the past decade, advances in genomics, structural biology, and synthetic biology have substantially revised our understanding of TA biosynthesis, leading to the identification of numerous key biosynthetic enzymes and evolutionary mechanisms. This review comprehensively summarizes current knowledge of TA biosynthesis from precursor formation to structurally diverse end products. We describe the pathway from putrescine to tropinone, the stereoselective metabolic branching mediated by Tropinone Reductases, and the downstream biosynthesis of medicinal tropane alkaloids, calystegines, and cocaine. Particular emphasis is placed on recent discoveries concerning catalytic mechanisms, structural determinants of substrate specificity, metabolic compartmentalization, and the convergent evolution of TA biosynthesis in Solanaceae and Erythroxylaceae. We further integrate advances in genomics, evolutionary biology, and metabolic engineering to highlight emerging strategies for microbial production and pathway redesign. By providing a comprehensive synthesis of recent progress and critical perspectives on unresolved questions, this review offers an updated framework for understanding TA biosynthesis and supports future research in plant specialized metabolism, synthetic biology, and natural product engineering.
Tropanes↗