Rethinking concepts of virulence with Neisseria gonorrhoeae
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Novobiocin primarily targets ParE in Neisseria gonorrhoeae
Multidrug-resistant Neisseria gonorrhoeae is a pathogenic bacterium that poses a public health concern. In this study, we aimed to elucidate the mode of action of the conventional antibiotic novobiocin, which has been selected as a leading compound for novel antigonococcal drugs. Unlike other previously studied bacteria strains, novobiocin-resistant N. gonorrhoeae strains have a mutation in the parE gene encoding DNA topoisomerase IV, strongly implying that the primary target of novobiocin is DNA topoisomerase IV and not DNA gyrase. The construction of genetically modified strains and structural biology analysis in silico suggest that this target discrepancy is from variations in the amino acid sequences in GyrB (Ile 78 in Escherichia coli, Met82 in N. gonorrhoeae) and ParE (Met 74 in E. coli, Ile76 in N. gonorrhoeae). This finding contributes to the development of drugs that target both GyrB and ParE enzymes to a similar extent.
Coevolution between marine Aeromonas and phages reveals temporal trade-off patterns of phage resistance and host population fitness
Coevolution of bacteria and phages is an important host and parasite dynamic in marine ecosystems, contributing to the understanding of bacterial community diversity. On the time scale, questions remain concerning what is the difference between phage resistance patterns in marine bacteria and how advantageous mutations gradually accumulate during coevolution. In this study, marine Aeromonas was co-cultured with its phage for 180 days and their genetic and phenotypic dynamics were measured every 30 days. We identified 11 phage resistance genes and classified them into three categories: lipopolysaccharide (LPS), outer membrane protein (OMP), and two-component system (TCS). LPS shortening and OMP mutations are two distinct modes of complete phage resistance, while TCS mutants mediate incomplete resistance by repressing the transcription of phage genes. The co-mutation of LPS and OMP was a major mode for bacterial resistance at a low cost. The mutations led to significant reductions in the growth and virulence of bacterial populations during the first 60 days of coevolution, with subsequent leveling off. Our findings reveal the marine bacterial community dynamics and evolutionary trade-offs of phage resistance during coevolution, thus granting further understanding of the interaction of marine microbes.
Informational ecosystems partially explain differences in socioenvironmental conceptual associations between U.S. American racial groups
Social groups represent a collective identity defined by a distinct consensus of concepts (e.g., ideas, values, and goals) whose structural relationship varies between groups. Here we set out to measure how a set of inter-concept semantic associations, comprising what we refer to as a concept graph, covaries between established social groups, based on racial identity, and how this effect is mediated by information ecosystems, contextualized as news sources. Group differences among racial identity (278 Black and 294 white Americans) and informational ecosystems (Left- and Right- leaning news sources) are present in subjective judgments of how the meaning of concepts such as healthcare, police, and voting relate to each other. These racial group differences in concept graphs were partially mediated by the bias of news sources that individuals get their information from. This supports the idea of groups being defined by common conceptual semantic relationships that partially arise from shared information ecosystems.
Metabolic crosstalk between the mitochondrion and the nucleus is essential for Toxoplasma gondii infection
Toxoplasma gondii, an intracellular pathogenic protist with a remarkable ability to infect a wide range of host cells, displays an equally exceptional design of its carbon metabolism. There are, however, critical gaps in our understanding of the metabolic network in T. gondii. We characterized the mito-nuclear metabolism and organelle coupling during its acute infection (lytic cycle). The major enzymes of the TCA cycle, i.e., citrate synthase (CS1), succinyl-CoA synthase alpha subunit (SCSα), succinate dehydrogenase (SDHA) and FAD malate dehydrogenase (MDH-FAD) located in the parasite mitochondrion support its asexual reproduction but are not needed for its survival. The SCSα and SDHA mutants are nearly avirulent in a mouse model, and they can protect the host against a lethal challenge infection. Genetic deletion of MDH-FAD dysregulated glucose-derived carbon flux, leading to a collapse of the mitochondrial membrane potential. The parasite also harbors a cytosolic isoform of MDH and a nuclear malic enzyme (ME) contributing to malate oxidation; however, only the latter is essential for the lytic cycle. Expression of ME in the nucleus is crucial for the parasite development. Besides, conditional knockdown of ME impairs the histone acetylation and disrupts the expression of several genes in tachyzoites. Our work discloses novel network design features of T. gondii and highlights the therapeutic and vaccination potential of the parasite metabolism.
Immunosurveillance of Candida albicans commensalism by the adaptive immune system
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