New genotoxin shows diversity of bacterial attack mechanisms

Bacteria make a wide range of toxic products that interact with eukaryotic cellular machinery in a precise way. These toxins interfere with key eukaryotic processes, such as cellular signalling components, and some directly attack the genome. Nougayrède and colleagues have recently identified a novel hybrid peptide-polyketide compound from Escherichia coli that leads to DNA damage. This novel compound is produced by pathogenic and, most interestingly, commensal isolates. Although it is not yet clear how the peptide-polyketide compound functions at the molecular level, it is possible that it contributes to bacterial pathogenesis and bacterially induced carcinogenesis.     

The role of ATP-binding cassette transporters in bacterial pathogenicity

The ATP-binding cassette transporter superfamily is present in all three domains of life. This ubiquitous class of integral membrane proteins have diverse biological functions, but their fundamental role involves the unidirectional translocation of compounds across cellular membranes in an ATP coupled process. The importance of this class of proteins in eukaryotic systems is well established as typified by their association with genetic diseases and roles in the multi-drug resistance of cancer. In stark contrast, the ABC transporters of prokaryotes have not been exhaustively investigated due to the sheer number of different roles and organisms in which they function. In this review, we examine the breadth of functions associated with microbial ABC transporters in the context of their contribution to bacterial pathogenicity and virulence.     

Genomic clues for defining bacterial pathogenicity

Genomic sequences are becoming available from both pathogenic and nonpathogenic bacteria. Here we analyze an increasing body of information available on the molecular mechanisms Salmonella typhimurium uses to cause disease, in order to divine clues for identifying sequences that play a role in pathogenesis in other bacterial pathogens.     

The diversity of organelle protein import mechanisms

It was once believed that common mechanisms underpin the transfer of proteins across the membrane systems of organelles such as mitochondria, chloroplasts and peroxisomes. Now that many of the core components of the translocases have been indentified, results discussed at a recent conference [Max-Delbrück-Centrum Symposium "Protein Transport and Stability"; Berlin, Germany; 21-26 March 2001. Organized by Thomas Sommer and Enno Hartmann.] stress just how diverse the mechanisms of transport into these organelles really are.     

Import of bacterial pathogenicity factors into mitochondria

Recent research on the mechanism underlying the interaction of bacterial pathogens with their host has shifted the focus to secreted microbial proteins affecting the physiology and innate immune response of the target cell. These proteins either traverse the plasma membrane via specific entry pathways involving host cell receptors or are directly injected via bacterial secretion systems into the host cell, where they frequently target mitochondria. The import routes of bacterial proteins are mostly unknown, whereas the effect of mitochondrial targeting by these proteins has been investigated in detail. For a number of them, classical leader sequences recognized by the mitochondrial protein import machinery have been identified. Bacterial outer membrane beta-barrel proteins can also be recognized and imported by mitochondrial transporters. Besides an obvious importance in pathogenicity, understanding import of bacterial proteins into mitochondria has a highly relevant evolutionary aspect, considering the endosymbiotic, proteobacterial origin of mitochondria. The review covers the current knowledge on the mitochondrial targeting and import of bacterial pathogenicity factors.     

Evolution of permease diversity and energy-coupling mechanisms with special reference to the bacterial phosphotransferase system

Different classes of apparently unrelated permeases couple different forms of energy to solute transport. While the energy coupling mechanisms utilized by the different permease classes are clearly distinct, it is proposed, based on structural comparisons, that many of these permeases possess transmembrane, hydrophobic domains which are evolutionarily related. Carriers may have arisen from transmembrane pore-forming proteins, and the protein constituents or domains which are specifically responsible for energy coupling may have had distinct origins. Thus, complex permeases may possess mosaic structures. This suggestion is substantiated by recent findings regarding the evolutionary origins of the bacterial phosphoenolpyruvate-dependent phosphotransferase system (PTS). Mechanistic implications of this proposal are presented.     

Tools to study molecular mechanisms of Aspergillus pathogenicity

The unique nature of Aspergillus fungi represents a challenge for scrutinizing the attributes that render these saprophytic microorganisms pathogenic or allergenic under certain environmental circumstances. Recent publication of the genomic sequence from an isolate of the major pathogen Aspergillus fumigatus denotes enormous progress in aiming at cellular features and gene products that contribute to its pathogenicity. Latest developments to study virulence-related characteristics comprise profiling techniques, conditional gene inactivation and precise manipulation of the genome by means of gene targeting. Advances in assessing the virulence potential of particular mutant strains in alternative test systems complement these approaches.     

Combined effects of zooplankton grazing and dispersal on the diversity and assembly mechanisms of bacterial metacommunities

Effects of dispersal and the presence of predators on diversity, assembly and functioning of bacterial communities are well studied in isolation. In reality, however, dispersal and trophic interactions act simultaneously and can therefore have combined effects, which are poorly investigated. We performed an experiment with aquatic metacommunities consisting of three environmentally different patches and manipulated dispersal rates among them as well as the presence or absence of the keystone species Daphnia magna. Daphnia magna reduced both local and regional diversity, whereas dispersal increased local diversity but decreased beta‐diversity having no net effect on regional diversity. Dispersal modified the assembly mechanisms of bacterial communities by increasing the degree of determinism. Additionally, the combination of the D. magna and dispersal increased the importance of deterministic processes, presumably because predator‐tolerant taxa were spread in the metacommunity via dispersal. Moreover, the presence of D. magna affected community composition, increased community respiration rates but did not affect bacterial production or abundance, whereas dispersal slightly increased bacterial production. In conclusion, our study suggests that predation by a keystone species such as D. magna and dispersal additively influence bacterial diversity, assembly processes and ecosystem functioning.     

异育银鲫败血病病原体的诊断及毒力和药敏实验

通过对合肥市某养殖基地发病的十余只异育银鲫的临床观察,经病原体分离培养与生理化鉴定,结果初步表明,该病病原体为嗜水气单胞菌;分离菌对多种抗菌素有敏感性;毒力实验证实,分离菌对小白鼠具有致病性。     

非编码RNA在胞内病原菌免疫逃逸与致病中的作用

非编码RNA(non-coding RNAs,ncRNAs)在细胞增殖、发育、分化、代谢、信号转导以及免疫调控中发挥重要调节作用。越来越多的研究证明,ncRNA在胞内病原菌的致病性和免疫逃逸中发挥重要调控作用。一方面ncRNA是细菌代谢、群体感应和毒力因子表达的调控因子,与胞内病原菌的致病性密切相关;另一方面ncRNA在调节宿主抗胞内病原菌免疫应答中发挥重要作用,深入研究ncRNA如何调节宿主免疫应答将有助于胞内菌免疫逃逸机制的研究。就非编码RNA在胞内病原菌免疫逃逸和致病中的作用作一综述。     

Clinical Clostridium difficile: clonality and pathogenicity locus diversity

Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings. The major virulence determinants are large clostridial toxins, toxin A (tcdA) and toxin B (tcdB), encoded within the pathogenicity locus (PaLoc). Isolates vary in pathogenicity from hypervirulent PCR-ribotypes 027 and 078 with high mortality, to benign non-toxigenic strains carried asymptomatically. The relative pathogenicity of most toxigenic genotypes is still unclear, but may be influenced by PaLoc genetic variant. This is the largest study of C. difficile molecular epidemiology performed to date, in which a representative collection of recent isolates (n = 1290) from patients with CDI in Oxfordshire, UK, was genotyped by multilocus sequence typing. The population structure was described using NeighborNet and ClonalFrame. Sequence variation within toxin B (tcdB) and its negative regulator (tcdC), was mapped onto the population structure. The 69 Sequence Types (ST) showed evidence for homologous recombination with an effect on genetic diversification four times lower than mutation. Five previously recognised genetic groups or clades persisted, designated 1 to 5, each having a strikingly congruent association with tcdB and tcdC variants. Hypervirulent ST-11 (078) was the only member of clade 5, which was divergent from the other four clades within the MLST loci. However, it was closely related to the other clades within the tcdB and tcdC loci. ST-11 (078) may represent a divergent formerly non-toxigenic strain that acquired the PaLoc (at least) by genetic recombination. This study focused on human clinical isolates collected from a single geographic location, to achieve a uniquely high density of sampling. It sets a baseline of MLST data for future comparative studies investigating genotype virulence potential (using clinical severity data for these isolates), possible reservoirs of human CDI, and the evolutionary origins of hypervirulent strains.