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PubMed1999

Antigen-driven CD4+ T cell and HIV-1 dynamics: residual viral replication under highly active antiretroviral therapy.

Antigen-induced stimulation of the immune system can generate heterogeneity in CD4+ T cell division rates capable of explaining the temporal patterns seen in the decay of HIV-1 plasma RNA levels during highly active antiretroviral therapy. Posttreatment increases in peripheral CD4+ T cell counts are consistent with a mathematical model in which host cell redistribution between lymph nodes and peripheral blood is a function of viral burden. Model fits to patient data suggest that, although therapy reduces HIV replication below replacement levels, substantial residual replication continues. This residual replication has important consequences for long-term therapy and the evolution of drug resistance and represents a challenge for future treatment strategies.

Anti-HIV Agents↗

PubMed2004

Identification of genes with fast-evolving regions in microbial genomes.

Complete sequences of multiple strains of the same microbial species provide an invaluable source for studying the evolutionary dynamics between orthologous genes over a relatively short time scale. Usually the intensity of the selection pressure is inferred from a comparison between the nonsynonymous substitution rate and the synonymous substitution rate. In this paper, we propose an alternative method for detecting genes with one or more fast-evolving regions from pairwise comparisons of orthologous genes. Our method looks for regions with overrepresented nonsynonymous mutations along the alignment, and requires a higher nonsynonymous evolution rate in those regions than the neutral evolution rate. It identifies gene targets under intensive selection pressure that are not detected from the conventional rate comparison analysis. For those identified genes with known annotations, most of them have a clear role in processes such as bacterial defense and host-pathogen interactions. Gene sets reported from our method provide a measure of the phenotypic divergence between two closely related genomes.

Amino Acid Sequence↗

PubMed1995

Strong function-related homology between the pore-forming colicins K and 5.

Sequence determination of the Escherichia coli colicin K determinant revealed identity with the E. coli colicin 5 determinant in the immunity and lysis proteins, strong homologies in the pore-forming region (93.7%) and the Tsx receptor-binding region (77%) of the colicins, and low levels of homology (20.3%) in the N-terminal region of the colicins. This latter region is responsible for the Tol-dependent uptake of colicin K and the Ton-dependent uptake of colicin 5 in the respective colicins. During evolution, the DNA encoding colicin activity and binding to the Tsx receptor was apparently recombined with two different DNA fragments that determined different uptake routes, leading to the differences observed in colicin K and colicin 5 import.

Amino Acid Sequence↗

PubMedDate not supplied

Role of chemotherapeutic antagonism in opportunistic infections.

The most widely-known anti-tumor drugs often induce marked immunosuppression which can give rise to one or more sepses. Anti-infection measures immediately applied can sometimes prove largely ineffective or even useless, the patient dying not as a result of the spread of the tumour but as a direct consequence of opportunistic infection. We postulate that antagonism between anti-tumour and antimicrobial drugs may also play an important part in this. By way of illustration of this hypothesis, we have studied the action of a number of known inhibitors of peptidoglycan synthesis and of DNA-gyrases on certain strains of Gram-positive and Gram-negative microorganisms cultured in medium containing various concentrations of some of the best-known anti-tumour antimetabolites. The experimental data show that antimicrobial and anti-tumour drugs can sometimes induce synergic or indifferent chemotherapeutic interactions with many bacteria, while in others the effect is antagonistic. In practice, the action of the drugs could lead to bacterial selectivity, which, in conjunction with immunosuppression and the presence of resistant strains, could favour the evolution of opportunistic infection.

Anti-Bacterial Agents↗

PubMed2005

Is antibiotic resistance a problem? A practical guide for hospital clinicians.

Antibiotic resistance is an important concern for patients, physicians, healthcare managers, and policymakers. Inappropriate antimicrobial prescribing fuels the evolution of resistance, while poor basic hygiene facilitates the spread of resistant microbes between patients and healthcare staff. The development of infection with a resistant pathogen may lead to poorer health and economic outcomes. The problem for the frontline clinician, however, is how to balance the responsibility of prudent prescribing with the risk of sub-optimally treating a patient who may be infected with a resistant pathogen. This article discusses how hospital physicians can use severity and risk factor assessment, and knowledge of local microbial epidemiology, to guide empiric antibiotic prescribing. Most patients hospitalised with a community acquired bacterial infection in the UK can still be managed with a traditional first line antibiotic(s). In contrast, regimens that account for resistance are often required in patients with hospital acquired infections, particularly if the patient is critically ill.

Anti-Bacterial Agents↗

PubMed1998

Cellular microbiology: cycling into the millennium.

Cellular microbiology is a newly developing science born from the realization that many different aspects of eukaryotic cell biology are targeted by microbial virulence mechanisms. One example of this is the emerging evidence that several bacteria can interfere, directly or indirectly, with the eukaryotic cell cycle. This article discusses the cell-cycle effects of bacterially generated molecules, their role in virulence and their possible therapeutic potential.

Adaptation, Physiological↗

PubMed2002

Analysis of macrolide-lincosamide-streptogramin B (MLS(B)) resistance determinant in strains of Clostridium difficile.

The macrolide-lincosamide-streptogramin B (MLSB) resistance determinants have been detected among Clostridia in both C. perfringens and C. difficile strains. Previous studies have shown that MLSB-resistant C. difficile strains can be differentiated by specific hybridizing bands using an erm(B) probe. A recent study has demonstrated that C. difficile 630, a strain highly resistant to clindamycin and erythromycin (MIC > or = 256 ml/L), showing a hybridizing band at 9.7 kb, contains two copies of an erm(B) gene. It was also hypothesized that C. difficile 630 erm(B) determinant has arisen from a progenitor, represented by the C. perfringens CP592 determinant, which contains only one copy of an erm(B) gene that differs from C. difficile 630 erm(B) for seven nucleotide substitutions. To investigate the possibility that C. difficile strains with hybridizing fragments of different molecular size have an erm(B) determinant not identical to the one described in C. difficile 630, we performed a genetic analysis on the erm(B) determinant in 18 C. difficile strains, isolated from different sources. The results showed a heterogeneity in erm(B) determinant: C. difficile strains with hybridizing bands at 7.3 or 3.7 kb contained only one erm(B) copy, whereas strains with a band at 9.7 kb had two copies. The majority of the toxigenic strains examined was characterized by only one erm(B) copy with a sequence identical to the one found in C. difficile 630 and a lower resistance level for erythromycin (MICs ranging from 16 to 24 ml/L). Differently, some strains had an erm(B) gene identical to the one found in C. perfringens CP592. PCR ribotyping and clustering analysis indicate that the examined resistant strains, except one, belong to the same genetic lineage. These results seem to support the hypothesis of the evolution of the C. difficile 630 erm(B) determinant. The functional significance of one or two copies of erm(B) gene in C. difficile strains should be further investigated.

Anti-Bacterial Agents↗

PubMed1997

A molecular view of microbial diversity and the biosphere.

Over three decades of molecular-phylogenetic studies, researchers have compiled an increasingly robust map of evolutionary diversification showing that the main diversity of life is microbial, distributed among three primary relatedness groups or domains: Archaea, Bacteria, and Eucarya. The general properties of representatives of the three domains indicate that the earliest life was based on inorganic nutrition and that photosynthesis and use of organic compounds for carbon and energy metabolism came comparatively later. The application of molecular-phylogenetic methods to study natural microbial ecosystems without the traditional requirement for cultivation has resulted in the discovery of many unexpected evolutionary lineages; members of some of these lineages are only distantly related to known organisms but are sufficiently abundant that they are likely to have impact on the chemistry of the biosphere.

Archaea↗

PubMed1998

Microbial diversity of soda lakes.

Soda lakes are highly alkaline extreme environments that form in closed drainage basins exposed to high evaporation rates. Because of the scarcity of Mg2+ and Ca2+ in the water chemistry, the lakes become enriched in CO3(2-) and Cl-, with pHs in the range 8 to > 12. Although there is a clear difference in prokaryotic communities between the hypersaline lakes where NaCl concentrations are > 15% w/v and more dilute waters, i.e., NaCl concentrations about 5% w/v, photosynthetic primary production appears to be the basis of all nutrient recycling. In both the aerobic and anaerobic microbial communities the major trophic groups responsible for cycling of carbon and sulfur have in general been identified. Systematic studies have shown that the microbes are alkaliphilic and many represent separate lineages within accepted taxa, while others show no strong relationship to known prokaryotes. Although alkaliphiles are widespread it seems probable that these organisms, especially those unique to the hypersaline lakes, evolved separately within an alkaline environment. Although present-day soda lakes are geologically quite recent, they have probably existed since archaean times, permitting the evolution of independent communities of alkaliphiles since an early period in the Earth's history.

Archaea↗

PubMed2003

Relations between bacterial biomass and carbon cycle in marine sediments: an early diagenetic model.

A new model for early diagenetic processes has been developed through a new formula explicitly accounting for microbial population dynamics. Following a mechanistic approach based on enzymatic reactions, a new model has been proposed for oxic mineralisation and denitrification. It incorporates the dynamics of bacterial metabolism. We find a general formula for inhibition processes of which some other mathematical expressions are particular cases. Moreover a fast numerical algorithm has been developed. It allows us to perform simulations of different diagenetic models in non-steady states. We use this algorithm to compare our model to a classical one (Soetaert et al., 1996). Dynamical evolutions of a perturbation of particulate organic carbon (POC) input are studied for both models. The results are very similar for stationary cases. But with variable inputs, the bacterial biomass dynamics brings about noticeable differences, and these are discussed.

Algorithms↗

PubMed2006

Bacteriophage migration via nematode vectors: host-parasite-consumer interactions in laboratory microcosms.

Pathogens vectored by nematodes pose serious agricultural, economic, and health threats; however, little is known of the ecological and evolutionary aspects of pathogen transmission by nematodes. Here we describe a novel model system with two trophic levels, bacteriophages and nematodes, each of which competes for bacteria. We demonstrate for the first time that nematodes are capable of transmitting phages between spatially distinct patches of bacteria. This model system has considerable advantages, including the ease of maintenance and manipulation at the laboratory bench, the ability to observe many generations in short periods, and the capacity to freeze evolved strains for later comparison to their ancestors. More generally, experimental studies of complex multispecies interactions, host-pathogen coevolution, disease dynamics, and the evolution of virulence may benefit from this model system because current models (e.g., chickens, mosquitoes, and malaria parasites) are costly to maintain, are difficult to manipulate, and require considerable space. Our initial explorations centered on independently assessing the impacts of nematode, bacterium, and phage population densities on virus migration between host patches. Our results indicated that virus transmission increases with worm density and host bacterial abundance; however, transmission decreases with initial phage abundance, perhaps because viruses eliminate available hosts before migration can occur. We discuss the microbial growth dynamics that underlie these results, suggest mechanistic explanations for nematode transmission of phages, and propose intriguing possibilities for future research.

Animals↗

PubMed2005

Hypermutability impedes cooperation in pathogenic bacteria.

When the supply of beneficial mutations limits adaptation, bacterial mutator alleles can reach high frequencies by hitchhiking with advantageous mutations. However, when populations are well adapted to their environments, the increased rate of deleterious mutations makes hypermutability selectively disadvantageous. Here, we consider a further cost of hypermutability: its potential to break down cooperation (group-beneficial behavior that is costly to the individual). This probably occurs for three reasons. First, an increased rate at which 'cheating' genotypes are generated; second, an increased probability of producing efficient cheats; and third, a decrease in relatedness (not addressed in the present study). We used Pseudomonas aeruginosa's production of extracellular iron-scavenging molecules, siderophores, to determine if cheating evolved more readily in mutator populations. Siderophore production is costly to individual bacteria but benefits all nearby cells. Siderophore-deficient cheats therefore have a selective advantage within populations. We observed the de novo evolution and subsequent increase in frequency of siderophore cheats within both wild-type and mutator populations for 200 generations. Cheats appeared and increased in frequency more rapidly in mutator populations. The presence of cheats was costly to the group, as shown by a negative correlation between cheat frequency and population density.

Colony Count, Microbial↗

PubMed2006

Phenothiazinium derivatives for pathogen inactivation in blood products.

Phenothiazine-based photosensitisers have been employed in photoantimicrobial research for nearly 80 years, both as lead and novel compounds. However, the main structural variations have mainly involved the auxochromic side chains and little has been reported concerning either peripheral substitution or structures with chromophores other than those of the phenothiazinium or annelated benzo[a]phenothiazinium type. In terms of application, the phenothiazinium series has featured commonly in cytology and cytopathology, as well as in haematological staining. The current work covers the evolution of improved photosensitisers based on the phenothiazine ring system, with particular reference to the field of pathogen inactivation, and the structural alteration of lead compounds such as methylene blue and Nile blue to yield improved photosensitisers for this important aspect of blood product safety.

Blood↗

PubMed1996

Control strategies for tuberculosis epidemics: new models for old problems.

Tuberculosis, although preventable and curable, causes more adult deaths than any other infectious disease. A theoretical framework for designing effective control strategies is developed and used to determine treatment levels for eradication, to assess the effects of noneradicating control, and to examine the global goals of the World Health Organization. The theory is extended to assess how suboptimal control programs contribute to the evolution of drug resistance. A new evaluation criterion is defined and used to suggest how control strategies can be improved. In order to control tuberculosis, treatment failure rates must be lower in developing countries than in developed countries.

Adult↗

PubMed2026

Genomic characterization of KPC-2 and NDM coproducing carbapenem-resistant Klebsiella pneumoniae in a hospital: discovery of ST1869 clone and a novel hybrid plasmid.

UNLABELLED: To characterize the plasmid architecture and molecular background of KPC-NDM coproducing carbapenem-resistant Klebsiella pneumoniae (KN-CRKP) in a South China hospital. Five KN-CRKP isolates were collected, including three from one patient. All underwent Illumina sequencing; two (ST11 and ST1869) additionally had Nanopore sequencing. Antimicrobial susceptibility testing strain sequence types, conjugation assays, resistance gene profiling, plasmid typing, genetic structure comparison, core-genome single nucleotide polymorphisms (SNPs) analysis, and plasmid clustering were performed. All isolates exhibited an imipenem minimum inhibitory concentration (MIC) of ≥128 µg/mL and harbored multiple resistance genes. One isolate (1/5) belonged to ST1869 and co-harbored blaKPC-2 and blaNDM-5. The blaNDM-5-carrying plasmid was a novel IncI1/X3 fusion plasmid that also carried blaCMY-42. Unlike several IncX3 plasmids carrying blaNDM in publicly available KN-CRKP genomes from South China, this IncI1/X3 hybrid lacked a complete conjugative transfer system. ST11 was the predominant clone (4/5), co-harboring blaKPC-2 and blaNDM-1. A rare genetic structure, ΔISKpn6-blaKPC-2-ISKpn28, was identified on IncFII plasmids carrying blaKPC-2. Plasmid clustering analysis of 126 comparative KN-CRKP genomes showed diverse sequence types and plasmid backgrounds associated with the KPC/NDM co-production pattern. The observed plasmid diversity and structural variation in KN-CRKP support continued genomic surveillance, with particular attention to the ST1869 clone, the novel IncI1/X3 hybrid plasmid harboring blaNDM-5 and blaCMY-42, and the rare "ΔISKpn6-blaKPC-2-ISKpn28" genetic structure. Expanded genomic data on KN-CRKP are needed to further elucidate its resistance mechanisms and plasmid evolutionary trajectories. IMPORTANCE: The co-production of KPC and NDM carbapenemases in Klebsiella pneumoniae poses a formidable threat to clinical antimicrobial therapy, as these enzymes confer resistance to virtually all β-lactam agents, including carbapenems. Here, we report novel genomic features of KN-CRKP in South China, including the emergence of the ST1869 clone, a unique IncI1/X3 hybrid plasmid harboring blaNDM-5 and blaCMY-42, and the rare ΔISKpn6-blaKPC-2-ISKpn28 genetic structure. These findings substantially expand current understanding of plasmid evolution and resistance gene dissemination in this region. The identification of diverse resistance mechanisms and clonal backgrounds supports enhanced genomic surveillance and infection-control awareness for pan-resistant Enterobacterales.

Plasmids↗

PubMed2000

Polyphosphate and phosphate pump.

In microbial cells, inorganic polyphosphate (polyP) plays a significant role in increasing cell resistance to unfavorable environmental conditions and in regulating different biochemical processes. polyP is a polyfunctional compound. The most important of its functions are the following: phosphate and energy reservation, cation sequestration and storage, membrane channel formation, participation in phosphate transport, involvement in cell envelope formation and function, gene activity control, regulation of enzyme activities, and a vital role in stress response and stationary-phase adaptation. The functions of polyP have changed greatly during the evolution of living organisms. In prokaryotes, the most important functions are as an energy source and a phosphate reserve. In eukaryotic microorganisms, the regulatory functions predominate. Therefore, a great difference is observed between prokaryotes and eukaryotes in their polyP-metabolizing enzymes. Some key prokaryotic enzymes are not present in eukaryotes, and conversely, eukaryotes have developed new polyP-metabolizing enzymes that are not present in prokaryotes. The synthesis and degradation of polyP in each specialized organelle and compartment of eukaryotic cells are mediated by different sets of enzymes. This is consistent with the endosymbiotic hypothesis of eukaryotic cell origin.

Biological Evolution↗

PubMedDate not supplied

[Ecological strategy of bacteria: specific nature of the problem].

An attempt is made to sum up the results of the many years of using the conception of ecological strategy in bacterial ecology. Taking into account the specificities of microorganisms and their natural selection and the coevolution of microorganisms within evolving microbial communities, an inference is derived that the ecological strategy of most bacteria is the sum of a number of particular canonical strategies, some of which are common to higher organisms. It is proposed to term these particular strategies ecological tactics. The author considers this review as a basis for discussion.

Adaptation, Biological↗

PubMedDate not supplied

[Water and antibioresistant bacteria: an ecological study (author's transl)].

The goal of this work is to describe the evolution of bacteria resistant to antibiotics in an aquatic environment and to compare their importance at different stages: human flora, sewage, surface water. Coliforms, fecal coliforms and Aeromonas are selected at test bacteria. The incidence of this difussion and influencing factors are discussed.

Aeromonas↗