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Lethality of MalE-LacZ hybrid protein shares mechanistic attributes with oxidative component of antibiotic lethality.

ABSTRACT: Downstream metabolic events can contribute to the lethality of drugs or agents that interact with a primary cellular target. In bacteria, the production of reactive oxygen species (ROS) has been associated with the lethal effects of a variety of stresses including bactericidal antibiotics, but the relative contribution of this oxidative component to cell death depends on a variety of factors. Experimental evidence has suggested that unresolvable DNA problems caused by incorporation of oxidized nucleotides into nascent DNA followed by incomplete base excision repair contribute to the ROS-dependent component of antibiotic lethality. Expression of the chimeric periplasmic-cytoplasmic MalE-LacZ72-47 protein is an historically important lethal stress originally identified during seminal genetic experiments that defined the SecY-dependent protein translocation system. Multiple, independent lines of evidence presented here indicate that the predominant mechanism for MalE-LacZ lethality shares attributes with the ROS-dependent component of antibiotic lethality. MalE-LacZ lethality requires molecular oxygen, and its expression induces ROS production. The increased susceptibility of mutants sensitive to oxidative stress to MalE-LacZ lethality indicates that ROS contribute causally to cell death rather than simply being produced by dying cells. Observations that support the proposed mechanism of cell death include MalE-LacZ expression being bacteriostatic rather than bactericidal in cells that overexpress MutT, a nucleotide sanitizer that hydrolyzes 8-oxo-dGTP to the monophosphate, or that lack MutM and MutY, DNA glycosylases that process base pairs involving 8-oxo-dGTP. Our studies suggest stress-induced physiological changes that favor this mode of ROS-dependent death.

SUBMITTER: Takahashi N

PROVIDER: S-EPMC5576823 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Lethality of MalE-LacZ hybrid protein shares mechanistic attributes with oxidative component of antibiotic lethality.

Takahashi Noriko N Gruber Charley C CC Yang Jason H JH Liu Xiaobo X Braff Dana D Yashaswini Chittampalli N CN Bhubhanil Sakkarin S Furuta Yoshikazu Y Andreescu Silvana S Collins James J JJ Walker Graham C GC

Proceedings of the National Academy of Sciences of the United States of America 20170809 34

Downstream metabolic events can contribute to the lethality of drugs or agents that interact with a primary cellular target. In bacteria, the production of reactive oxygen species (ROS) has been associated with the lethal effects of a variety of stresses including bactericidal antibiotics, but the relative contribution of this oxidative component to cell death depends on a variety of factors. Experimental evidence has suggested that unresolvable DNA problems caused by incorporation of oxidized n ...[more]

PMID: 28794281

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Project description:AbstractDespite strong selective pressures inherent in competition for mates, in species with non-resource-based mating systems males commonly engage in non-agonistic interactions with same-sex visitors at display arenas. Bowerbirds perform courtship dances on elaborate display structures - known as bowers - that are built and defended by one resident male. Several reports have suggested that bower owners tolerate the presence of specific male visitors at their display arenas, referred to here as 'subordinates'. Subordinate males may learn the skills required for successful sexual signalling via prolonged social interactions at adults' arenas, but little is known about whether courtship proficiency changes with experience and/or whether subordinates actively contribute to enhancing the resident male's mating success. In this study, we investigated male-male associations in wild spotted bowerbirds (Ptilonorhynchus maculatus). We first sought to determine whether courtship behaviour differs based on bower ownership status. We then examined whether social interactions between bower owners and subordinate males may qualify as courtship coalitions. Our analysis of courtship postural components did not reveal differences in timing or relative occurrence of postural components between subordinate males and bower owners, whereas we found evidence that male-male associations in spotted bowerbirds may provide an example of rudimentary courtship coalitions. In particular, higher subordinate attendance is associated with lower destruction rates by neighbouring rivals and with overall higher mating success, and male pairs are stable in subsequent years. This study provides novel information about social dynamics among male bowerbirds, and further insights into the evolution of coalitionary behaviour in male displays.Significance statementSame-sex associations between established males and subordinate visitors on display arenas are common in birds, yet poorly understood. Using video recordings from a population of wild spotted bowerbirds, Ptilonorhynchus maculatus, we performed a quantitative analysis on motor courtship components across males, and on their social interactions on display arenas to investigate the nature of male-male partnerships. Our results showed that motor courtship performance in subordinate visitors is not suggestive of an early ontogenetic stage, as previously speculated. Moreover, though bower 'owners' and subordinate males do not coordinate their behaviour during courtship or bower building, male-male partnerships may qualify as a rudimentary or incipient form of courtship coalitions. Subordinate males are tolerated at bowers, the magnitude of subordinate attendance correlates with owner males' mating success, and repeated interactions between individuals reveal consistent partner associations.Supplementary informationThe online version contains supplementary material available at 10.1007/s00265-022-03200-x.

Dataset Information

Lethality of MalE-LacZ hybrid protein shares mechanistic attributes with oxidative component of antibiotic lethality.

Publications

Lethality of MalE-LacZ hybrid protein shares mechanistic attributes with oxidative component of antibiotic lethality.

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