SEX - Word Related Documents




#
Rank
Similarity
Title + Abs.
Year
PMID
012345
375800.9945The effects of hormones on sex differences in infection: from genes to behavior. Males of many species are more susceptible than females to infections caused by parasites, fungi, bacteria, and viruses. One proximate cause of sex differences in infection is differences in endocrine-immune interactions. Specifically, males may be more susceptible to infection than females because sex steroids, specifically androgens in males and estrogens in females, modulate several aspects of host immunity. It is, however, becoming increasingly more apparent that in addition to affecting host immunity, sex steroid hormones alter genes and behaviors that influence susceptibility and resistance to infection. Thus, males may be more susceptible to infection than females not only because androgens reduce immunocompetence, but because sex steroid hormones affect disease resistance genes and behaviors that make males more susceptible to infection. Consideration of the cumulative effects of sex steroid hormones on susceptibility to infection may serve to clarify current discrepancies in the literature and offer alternative hypotheses to the view that sex steroid hormones only alter susceptibility to infection via changes in host immune function.200010940438
823410.9942Contradictory roles for antibody and complement in the interaction of Brucella abortus with its host. The ability of serum complement to kill bacteria has been linked to host resistance to Gram-negative bacteria. A mechanism for killing extracellular organisms during early invasion, following release from infected phagocytic cells, or during bacteremia would contribute to a host's ability to resist disease. In fact, the ability of serum complement to kill bacteria has been linked to disease resistance. Brucella abortus are Gram-negative intracellular pathogens. Resistance to these bacteria involves the coordinated activities of the cellular and humoral immune systems. The existence of serum-resistant forms of B. abortus has been established, and it has been shown that these bacteria can resist the killing action of complement even in the presence of specific antibody. Antibody is usually necessary for complement-mediated killing of smooth (virulent) forms of Gram-negative bacteria. An anomolous situation exists with some isolates of smooth B. abortus. Sera containing high titers of specific antibody do not support killing unless they are diluted. In the bovine, this phenomenon is associated with IgG1 and IgG2 antibodies. This finding may account for the lack of positive correlation between antibody levels and resistance to disease, which has led, perhaps wrongly, to the idea that antibody and complement are not important in resistance to brucellosis. Available evidence suggests that antibody may have contradictory roles in the interactions between a host and bacteria. Avirulent (rough) forms of the organism would be rapidly killed by complement shortly after invasion, but serum-resistant smooth forms of the organism would survive and invade resident phagocytic cells. During the process of invasion and phagocytosis, the bacteria would initiate an immune response. With time, some B. abortus organisms would be released from infected phagocytic cells. In the early stages of this process, the bacteria would encounter IgM antibody and low concentrations of IgG antibody. These would cause complement-mediated killing, and infection would be restricted to resident phagocytic cells. However, the immune response to B. abortus antigens would be intensified, and IgG antibody levels would increase. High concentrations of antibody do no support complement-mediated killing of extracellular B. abortus, but the bacteria would be opsonized by antibody and complement component fragments. This would lead to increased phagocytosis of extracellular B. abortus as they appear, and concomitant extension of disease. Because of high levels of antibody would block complement-mediated killing of B. abortus, resistance to disease at this point would be dependent on cell-mediated immunity.19958845060
826520.9941Mathematical modelling of CRISPR-Cas system effects on biofilm formation. Clustered regularly interspaced short palindromic repeats (CRISPR), linked with CRISPR associated (Cas) genes, can confer adaptive immunity to bacteria, against bacteriophage infections. Thus from a therapeutic standpoint, CRISPR immunity increases biofilm resistance to phage therapy. Recently, however, CRISPR-Cas genes have been implicated in reducing biofilm formation in lysogenized cells. Thus CRISPR immunity can have complex effects on phage-host-lysogen interactions, particularly in a biofilm. In this contribution, we develop and analyse a series of dynamical systems to elucidate and disentangle these interactions. Two competition models are used to study the effects of lysogens (first model) and CRISPR-immune bacteria (second model) in the biofilm. In the third model, the effect of delivering lysogens to a CRISPR-immune biofilm is investigated. Using standard analyses of equilibria, stability and bifurcations, our models predict that lysogens may be able to displace CRISPR-immune bacteria in a biofilm, and thus suggest strategies to eliminate phage-resistant biofilms.201728426329
941130.9939The evolutionary dynamics of male-killers and their hosts. Male-killing bacteria are cytoplasmic sex-ratio distorters that are transmitted vertically through females of their insect hosts. The killing of male hosts by their bacteria is thought to be an adaptive bacterial trait because it augments the fitness of female hosts carrying clonal relatives of those bacteria. Here we attempt to explain observations of multiple male-killers in natural host populations. First we show that such male-killer polymorphism cannot be explained by a classical model of male-killing. We then show that more complicated models incorporating the evolution of resistance in hosts can explain male-killer polymorphism. However, this is only likely if resistance genes are very costly. We also consider the long-term evolutionary dynamics of male-killers, and show that evolution towards progressively more 'efficient' male-killers can be thwarted by the appearance of host resistance. The presence of a resistance gene can allow a less efficient male-killer to outcompete its rival and hence reverse the trend towards more efficient transmission and reduced metabolic load on the host.200010762384
946840.9939Mendelian traits that confer predisposition or resistance to specific infections in humans. Mutations in human genes involved in immunity are increasingly recognised. Most are associated with conventional primary immunodeficiencies, which confer Mendelian predisposition to multiple infectious diseases. Recently, there has been much study of monogenic traits that do not confer such a broad vulnerability. Defects in several genes confer predisposition to infection with specific bacteria and viruses in otherwise healthy individuals. Mutations in other genes even confer resistance to specific pathogens, with no detectable decrease in fitness. These 'experiments of nature' reveal surprising specific interactions between certain human genes and microbial pathogens.200616765581
936550.9938Hypermutability and compensatory adaptation in antibiotic-resistant bacteria. Hypermutable (mutator) bacteria have been associated with the emergence of antibiotic resistance. A simple yet untested prediction is that mutator bacteria are able to compensate more quickly for pleiotropic fitness costs often associated with resistance, resulting in the maintenance of resistance in the absence of antibiotic selection. By using experimental populations of a wild-type and a mutator genotype of the pathogenic bacterium Pseudomonas aeruginosa, we show that mutator bacteria can evolve resistance to antibiotics more rapidly than wild-type bacteria and, crucially, that mutators are better able to compensate for the fitness cost of resistance, to the extent that all costs of resistance were entirely compensated for in mutators. When competed against immigrant antibiotic-susceptible bacteria in the absence of antibiotics, antibiotic resistance remained at a high level in mutator populations but disappeared in wild-type populations. These results suggest that selection for mutations that offset the fitness cost associated with antibiotic resistance may help to explain the high frequency of mutator bacteria and antibiotic resistance observed in chronic infections.201020624092
820260.9937Interaction between bacteriophage DMS3 and host CRISPR region inhibits group behaviors of Pseudomonas aeruginosa. Bacteriophage infection has profound effects on bacterial biology. Clustered regular interspaced short palindromic repeats (CRISPRs) and cas (CRISPR-associated) genes are found in most archaea and many bacteria and have been reported to play a role in resistance to bacteriophage infection. We observed that lysogenic infection of Pseudomonas aeruginosa PA14 with bacteriophage DMS3 inhibits biofilm formation and swarming motility, both important bacterial group behaviors. This inhibition requires the CRISPR region in the host. Mutation or deletion of five of the six cas genes and one of the two CRISPRs in this region restored biofilm formation and swarming to DMS3 lysogenized strains. Our observations suggest a role for CRISPR regions in modifying the effects of lysogeny on P. aeruginosa.200918952788
936670.9937Impact of bacterial mutation rate on coevolutionary dynamics between bacteria and phages. Mutator bacteria are frequently found in natural populations of bacteria and although coevolution with parasitic viruses (phages) is thought to be one reason for their persistence, it remains unclear how the presence of mutators affects coevolutionary dynamics. We hypothesized that phages must themselves adapt more rapidly or go extinct, in the face of rapidly evolving mutator bacteria. We compared the coevolutionary dynamics of wild-type Pseudomonas fluorescens SBW25 with a lytic phage to the dynamics of an isogenic mutator of P. fluorescens SBW25 together with the same phage. At the beginning of the experiment both wild-type bacteria and mutator bacteria coevolved with phages. However, mutators rapidly evolved higher levels of sympatric resistance to phages. The phages were unable to "keep-up" with the mutator bacteria, and these rates of coevolution declined to less than the rates of coevolution between the phages and wild-type bacteria. By the end of the experiment, the sympatric resistance of the mutator bacteria was not significantly different to the sympatric resistance of the wild-type bacteria. This suggests that the importance of mutators in the coevolutionary interactions with a particular phage population is likely to be short-lived. More generally, the results demonstrate that coevolving enemies may escape from Red-Queen dynamics.201020497216
823180.9937The evolutionary atavistic endotoxin and neoplastic growth. A hypothesis on the potential role of atavistic endotoxin in carcinogenesis is proposed. The presence of an antigen identical to the endotoxin of gram-negative bacteria in tumour cells is confirmed by IgM class natural specific antibodies to endotoxin (IgMNAE) in rats by immunizing them with rat tumour tissue extracts. Rat normal tissue extracts do not increase the endogenous level of natural immunity to endotoxin, indicating the absence of a foreign antigen such as endotoxin in normal cells which are naturally devoid also of other parasitic features such as invasiveness and metastases, whereas tumour cells, during a prolonged latent period of carcinogenesis, acquire resistance to harmful factors, lose most of their genetic, antigenic, morphological and biochemical properties and become parasitic so as to survive in unfavourable conditions. With the regression of the mentioned properties of cells to the atavistic parasitic state, the synthesis of dormant endotoxin is activated together with an enhanced expression of evolutionary resistance-related genes and oncogenes. Atavistic endotoxin, produced and secreted by proliferating tumour cells, should cause chronic cachexia and septic states in cancer patients, similarly as in cases of endotoxemic septic shock where the endotoxin of gram-negative bacteria is the main pathogenic factor. Thus, the implications of the hypothesis indicate the diagnostic as well as prognostic and preventive significance of evolutionary atavistic endotoxin and also of endotoxin from gram-negative bacteria in human cancers. Natural specific antibodies to endotoxin can be helpful in creating new immunotherapeutic methods.201120943325
923690.9936Mutant bacteriophages, Frank Macfarlane Burnet, and the changing nature of "genespeak" in the 1930s. In 1936, Frank Macfarlane Burnet published a paper entitled "Induced lysogenicity and the mutation of bacteriophage within lysogenic bacteria," in which he demonstrated that the introduction of a specific bacteriophage into a bacterial strain consistently and repeatedly imparted a specific property - namely the resistance to a different phage - to the bacterial strain that was originally susceptible to lysis by that second phage. Burnet's explanation for this change was that the first phage was causing a mutation in the bacterium which rendered it and its successive generations of offspring resistant to lysogenicity. At the time, this idea was a novel one that needed compelling evidence to be accepted. While it is difficult for us today to conceive of mutations and genes outside the context of DNA as the physico-chemical basis of genes, in the mid 1930s, when this paper was published, DNA's role as the carrier of hereditary information had not yet been discovered and genes and mutations were yet to acquire physical and chemical forms. Also, during that time genes were considered to exist only in organisms capable of sexual modes of replication and the status of bacteria and viruses as organisms capable of containing genes and manifesting mutations was still in question. Burnet's paper counts among those pieces of work that helped dispel the notion that genes, inheritance and mutations were tied to an organism's sexual status. In this paper, I analyze the implications of Burnet's paper for the understanding of various concepts - such as "mutation," and "gene," - at the time it was published, and how those understandings shaped the development of the meanings of these terms and our modern conceptions thereof.201020665082
9196100.9936Lessons from gene knockouts. The authors describe the technique for the application of homologous recombination in embryonic stem cells, which is now widely used to engineer mice which carry specific knockouts of genes. A summary is given of some of the knowledge of the pathogenesis of and resistance to infections with parasites, bacteria, or viruses which has accumulated during recent years, based on the investigation of knockout mice. Special emphasis is placed on knockout animals which lack components of the cytokine network, lack genes which are critical for the correct presentation of antigens or are deficient in different immune cell subsets. In addition, a brief explanation is offered of the possibilities for inducing targeted deletions or mutations in genes of livestock species (e.g., by nuclear transfer or by mutagenesis using the alkylating agent N-ethyl-N-nitrosourea) which could lead to the breeding of animals which are resistant to infectious diseases in the future.19989638823
9424110.9936The role of bacteria as a local defence mechanism in the ear, nose and throat. The mucosae of the oro-nasopharynx in man are asymptomatically colonised by a commensal flora. This commensal flora consists largely of non-pathogenic bacteria but potentially pathogenic bacteria, such as S. pneumoniae, H. influenzae, M. catarrhalis can also be part of it. The commensal flora can be affected by host factors such as age or antibiotic usage but will in itself also affect its host. In addition to being a source of resistance genes it will also protect the host against exogenous, non-commensal pathogens. This protective effect is the result of three characteristics of the commensal flora. The commensal flora will hinder the establishment of new pathogens on the mucosa (termed colonisation resistance), it will especifically stimulate the immune system and it will induce formation of protective antibodies.200011082758
9202120.9936Microbial avirulence determinants: guided missiles or antigenic flak? SUMMARY Avirulence (avr) determinants are incompatibility factors which elicit host plant defence responses in a gene-for-gene manner. They are produced by fungi, bacteria and viruses, and their recognition by resistance genes has been extensively studied for decades. But why should a microbe keep a molecule that allows it to be recognized? One argument is that avr genes perform some essential function and must be kept despite giving the pathogen away. Many bacterial avr determinants have been shown to be effectors, which contribute to virulence and aggressiveness. If this were always the case, mutants lacking these essential molecules would be at a serious disadvantage. Some disadvantage has been shown for a small number, but for the majority there is no effect on virulence. This has been explained by functional redundancy for bacterial and fungal avr determinants, with other molecules compensating for the deletion of these essential genes. However, this argument is counter-intuitive because by definition these individual genes are no longer essential; so why keep them? With increasing numbers of avr genes being identified, efforts to elucidate their function are increasing. In this review, we take stock of the accumulating literature, and consider what the real function of avr determinants might be.200520565679
9238130.9936Sexual isolation and speciation in bacteria. Like organisms from all other walks of life, bacteria are capable of sexual recombination. However, unlike most plants and animals, bacteria recombine only rarely, and when they do they are extremely promiscuous in their choice of sexual partners. There may be no absolute constraints on the evolutionary distances that can be traversed through recombination in the bacterial world, but interspecies recombination is reduced by a variety of factors, including ecological isolation, behavioral isolation, obstacles to DNA entry, restriction endonuclease activity, resistance to integration of divergent DNA sequences, reversal of recombination by mismatch repair, and functional incompatibility of recombined segments. Typically, individual bacterial species are genetically variable for most of these factors. Therefore, natural selection can modulate levels of sexual isolation, to increase the transfer of genes useful to the recipient while minimizing the transfer of harmful genes. Interspecies recombination is optimized when recombination involves short segments that are just long enough to transfer an adaptation, without co-transferring potentially harmful DNA flanking the adaptation. Natural selection has apparently acted to reduce sexual isolation between bacterial species. Evolution of sexual isolation is not a milestone toward speciation in bacteria, since bacterial recombination is too rare to oppose adaptive divergence between incipient species. Ironically, recombination between incipient bacterial species may actually foster the speciation process, by prohibiting one incipient species from out-competing the other to extinction. Interspecific recombination may also foster speciation by introducing novel gene loci from divergent species, allowing invasion of new niches.200212555790
8354140.9936Are inflammatory phagocytes responsible for resistance to facultative intracellular bacteria? At least 38 deaths from listeriosis in the United States in recent months have drawn attention to how little we know about resistance to facultative intracellular bacteria. Much more is known about resistance to obligate intracellular parasites. Macrophages, activated by T cell-derived macrophage activating factors (MAF), are able to kill obligate intracellular parasites and tumor cells(1-10) including Leishmania, certain trypanosomes, Toxoplasma, the obligate intracellular bacterium Rickettsia, and perhaps bacteria such as mycobacteria and Legionella. However, macrophages, stimulated by MAF, may not be the only host cells which can defend against infection by facultative intracellular bacteria such as Salmonella typhimurium or Listeria monocytogenes. Six different observations made by Priscilla Campbell and colleagues, and by others, suggest that it is not the so-called 'activated' macrophage which is primarily responsible for resistance against facultative intracellular bacteria. Rather, she proposes that an early inflammatory cell recently recruited in response to an inflammatory stimulus - a cell whose presence seems to be under the control of immunologically-specific T cells - plays a critical role in resistance to infection by these organisms.198625289573
9691150.9936Defining pathogenic bacterial species in the genomic era. Actual definitions of bacterial species are limited due to the current criteria of definition and the use of restrictive genetic tools. The 16S ribosomal RNA sequence, for example, has been widely used as a marker for phylogenetic analyses; however, its use often leads to misleading species definitions. According to the first genetic studies, removing a certain number of genes from pathogenic bacteria removes their capacity to infect hosts. However, more recent studies have demonstrated that the specialization of bacteria in eukaryotic cells is associated with massive gene loss, especially for allopatric endosymbionts that have been isolated for a long time in an intracellular niche. Indeed, sympatric free-living bacteria often have bigger genomes and exhibit greater resistance and plasticity and constitute species complexes rather than true species. Specialists, such as pathogenic bacteria, escape these bacterial complexes and colonize a niche, thereby gaining a species name. Their specialization allows them to become allopatric, and their gene losses eventually favor reductive genome evolution. A pathogenic species is characterized by a gene repertoire that is defined not only by genes that are present but also by those that are lacking. It is likely that current bacterial pathogens will disappear soon and be replaced by new ones that will emerge from bacterial complexes that are already in contact with humans.201021687765
9233160.9936The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Bacteria and Archaea have developed several defence strategies against foreign nucleic acids such as viral genomes and plasmids. Among them, clustered regularly interspaced short palindromic repeats (CRISPR) loci together with cas (CRISPR-associated) genes form the CRISPR/Cas immune system, which involves partially palindromic repeats separated by short stretches of DNA called spacers, acquired from extrachromosomal elements. It was recently demonstrated that these variable loci can incorporate spacers from infecting bacteriophages and then provide immunity against subsequent bacteriophage infections in a sequence-specific manner. Here we show that the Streptococcus thermophilus CRISPR1/Cas system can also naturally acquire spacers from a self-replicating plasmid containing an antibiotic-resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic-resistance genes provide a novel means to naturally select bacteria that cannot uptake and disseminate such genes. We also provide in vivo evidence that the CRISPR1/Cas system specifically cleaves plasmid and bacteriophage double-stranded DNA within the proto-spacer, at specific sites. Our data show that the CRISPR/Cas immune system is remarkably adapted to cleave invading DNA rapidly and has the potential for exploitation to generate safer microbial strains.201021048762
8350170.9936A Physiological Basis for Nonheritable Antibiotic Resistance. Antibiotics constitute one of the cornerstones of modern medicine. However, individuals may succumb to a bacterial infection if a pathogen survives exposure to antibiotics. The ability of bacteria to survive bactericidal antibiotics results from genetic changes in the preexisting bacterial genome, from the acquisition of genes from other organisms, and from nonheritable phenomena that give rise to antibiotic tolerance. Nonheritable antibiotic tolerance can be exhibited by a large fraction of the bacterial population or by a small subpopulation referred to as persisters. Nonheritable resistance to antibiotics has been ascribed to the activity of toxins that are part of toxin-antitoxin modules, to the universal energy currency ATP, and to the signaling molecule guanosine (penta) tetraphosphate. However, these molecules are dispensable for nonheritable resistance to antibiotics in many organisms. By contrast, nutrient limitation, treatment with bacteriostatic antibiotics, or expression of genes that slow bacterial growth invariably promote nonheritable resistance. We posit that antibiotic persistence results from conditions promoting feedback inhibition among core cellular processes, resulting phenotypically in a slowdown or halt in bacterial growth.202032546621
241180.9936A color-based competition assay for studying bacterial stress responses in Micrococcus luteus. Competition assays measure differences between populations of bacteria after stress adaptation, populations of different bacteria and mutations in antibiotic resistance genes. We have developed a competition-based assay to evaluate if genes upregulated under starvation are important for bacterial survival. Stress responses are critical for survival in non-pathogenic and pathogenic bacteria alike including Mycobacterium tuberculosis, Enterococcus fecaelis, Escherichia coli and Staphylococcus aureus. Unfortunately, most stress-survival proteins are poorly understood because suitable model bacteria and techniques are limited. To address this problem, we have engineered Micrococcus luteus NCTC 2665 (M. luteus) for competition assays by inactivating the sarcinaxanthin biosynthesis gene crtE (ΔcrtE), changing M. luteus colonies from yellow to white. This change allows easy identification in mixed cultures. The crtE knockout is relatively neutral for growth in complex and minimal acetate media and shows a measured fitness of one in competition with yellow wild-type bacteria. The ΔcrtE M. luteus competition assay identified a competition defect in a M. luteus strain when a specific universal stress protein was inactivated, suggesting a negative survival phenotype for this protein. We anticipate this competition assay can identify defects in other gene knockouts and mutational studies in M. luteus and will enhance our understanding of bacterial survival mechanisms.201930865770
9232190.9936CRISPR interference can prevent natural transformation and virulence acquisition during in vivo bacterial infection. Pathogenic bacterial strains emerge largely due to transfer of virulence and antimicrobial resistance genes between bacteria, a process known as horizontal gene transfer (HGT). Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci of bacteria and archaea encode a sequence-specific defense mechanism against bacteriophages and constitute a programmable barrier to HGT. However, the impact of CRISPRs on the emergence of virulence is unknown. We programmed the human pathogen Streptococcus pneumoniae with CRISPR sequences that target capsule genes, an essential pneumococcal virulence factor, and show that CRISPR interference can prevent transformation of nonencapsulated, avirulent pneumococci into capsulated, virulent strains during infection in mice. Further, at low frequencies bacteria can lose CRISPR function, acquire capsule genes, and mount a successful infection. These results demonstrate that CRISPR interference can prevent the emergence of virulence in vivo and that strong selective pressure for virulence or antibiotic resistance can lead to CRISPR loss in bacterial pathogens.201222901538