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906200.9660Biological cost of pyocin production during the SOS response in Pseudomonas aeruginosa. LexA and two structurally related regulators, PrtR and PA0906, coordinate the Pseudomonas aeruginosa SOS response. RecA-mediated autocleavage of LexA induces the expression of a protective set of genes that increase DNA damage repair and tolerance. In contrast, RecA-mediated autocleavage of PrtR induces antimicrobial pyocin production and a program that lyses cells to release the newly synthesized pyocin. Recently, PrtR-regulated genes were shown to sensitize P. aeruginosa to quinolones, antibiotics that elicit a strong SOS response. Here, we investigated the mechanisms by which PrtR-regulated genes determine antimicrobial resistance and genotoxic stress survival. We found that induction of PrtR-regulated genes lowers resistance to clinically important antibiotics and impairs the survival of bacteria exposed to one of several genotoxic agents. Two distinct mechanisms mediated these effects. Cell lysis genes that are induced following PrtR autocleavage reduced resistance to bactericidal levels of ciprofloxacin, and production of extracellular R2 pyocin was lethal to cells that initially survived UV light treatment. Although typically resistant to R2 pyocin, P. aeruginosa becomes transiently sensitive to R2 pyocin following UV light treatment, likely because of the strong downregulation of lipopolysaccharide synthesis genes that are required for resistance to R2 pyocin. Our results demonstrate that pyocin production during the P. aeruginosa SOS response carries both expected and unexpected costs.201425022851
843210.9654A 0D-2D Heterojunction Bismuth Molybdate-Anchored Multifunctional Hydrogel for Highly Efficient Eradication of Drug-Resistant Bacteria. Due to the increasing antibiotic resistance and the lack of broad-spectrum antibiotics, there is an urgent requirement to develop fresh strategies to combat multidrug-resistant pathogens. Herein, defect-rich bismuth molybdate heterojunctions [zero-dimensional (0D) Bi(4)MoO(9)/two-dimensional (2D) Bi(2)MoO(6), MBO] were designed for rapid capture of bacteria and synergistic photocatalytic sterilization. The as-prepared MBO was experimentally and theoretically demonstrated to possess defects, heterojunctions, and irradiation triple-enhanced photocatalytic activity for efficient generation of reactive oxygen species (ROS) due to the exposure of more active sites and separation of effective electron-hole pairs. Meanwhile, dopamine-modified MBO (pMBO) achieved a positively charged and rough surface, which conferred strong bacterial adhesion and physical penetration to the nanosheets, effectively trapping bacteria within the damage range and enhancing ROS damage. Based on this potent antibacterial ability of pMBO, a multifunctional hydrogel consisting of poly(vinyl alcohol) cross-linked tannic acid-coated cellulose nanocrystals (CPTB) and pMBO, namely CPTB@pMBO, is developed and convincingly effective against methicillin-resistant Staphylococcus aureus in a mouse skin infection model. In addition, the strategy of combining a failed beta-lactam antibiotic with CPTB@pMBO to photoinactivation with no resistance observed was developed, which presented an idea to address the issue of antibiotic resistance in bacteria and to explore facile anti-infection methods. In addition, CPTB@pMBO can reduce excessive proteolysis of tissue and inflammatory response by regulating the expression of genes and pro-inflammatory factors in vivo, holding great potential for the effective treatment of wound infections caused by drug-resistant bacteria.202337531599
886020.9651Antibiotic in myrrh from Commiphora molmol preferentially kills nongrowing bacteria. AIM: To demonstrate that myrrh oil preferentially kills nongrowing bacteria and causes no resistance development. METHOD: Growth inhibition was determined on regular plates or plates without nutrients, which were later overlaid with soft agar containing nutrients to continue growth. Killing experiments were done in broth and in buffer without nutrients. RESULTS: Bacterial cells were inhibited preferentially in the absence of nutrients or when growth was halted by a bacteriostatic antibiotic. After five passages in myrrh oil, surviving colonies showed no resistance to the antibiotic. CONCLUSION: Myrrh oil has the potential to be a commercially viable antibiotic that kills persister cells and causes no resistance development. This is a rare example of an antibiotic that can preferentially kill nongrowing bacteria.202032257371
910730.9650A versatile pH-responsive peptide based dynamic biointerface for tracking bacteria killing and infection resistance. Herein we reported a versatile dynamic biointerface based on pH-responsive peptide self-assembly and disassembly to capture the bacteria to avoid bacteria further infected tissue around that can release peptides from the surface in a slightly acidic environment to kill the bacteria with the specificity. The exposed biointerface still presented infection resistance.202134350905
57540.9650Identification and characterization of uvrA, a DNA repair gene of Deinococcus radiodurans. Deinococcus radiodurans is extraordinarily resistant to DNA damage, because of its unusually efficient DNA repair processes. The mtcA+ and mtcB+ genes of D. radiodurans, both implicated in excision repair, have been cloned and sequenced, showing that they are a single gene, highly homologous to the uvrA+ genes of other bacteria. The Escherichia coli uvrA+ gene was expressed in mtcA and mtcB strains, and it produced a high degree of complementation of the repair defect in these strains, suggesting that the UvrA protein of D. radiodurans is necessary but not sufficient to produce extreme DNA damage resistance. Upstream of the uvrA+ gene are two large open reading frames, both of which are directionally divergent from the uvrA+ gene. Evidence is presented that the proximal of these open reading frames may be irrB+.19968955293
874050.9646Nitrite reductase activity of sulphate-reducing bacteria prevents their inhibition by nitrate-reducing, sulphide-oxidizing bacteria. Sulphate-reducing bacteria (SRB) can be inhibited by nitrate-reducing, sulphide-oxidizing bacteria (NR-SOB), despite the fact that these two groups are interdependent in many anaerobic environments. Practical applications of this inhibition include the reduction of sulphide concentrations in oil fields by nitrate injection. The NR-SOB Thiomicrospira sp. strain CVO was found to oxidize up to 15 mM sulphide, considerably more than three other NR-SOB strains that were tested. Sulphide oxidation increased the environmental redox potential (Eh) from -400 to +100 mV and gave 0.6 nitrite per nitrate reduced. Within the genus Desulfovibrio, strains Lac3 and Lac6 were inhibited by strain CVO and nitrate for the duration of the experiment, whereas inhibition of strains Lac15 and D. vulgaris Hildenborough was transient. The latter had very high nitrite reductase (Nrf) activity. Southern blotting with D. vulgaris nrf genes as a probe indicated the absence of homologous nrf genes from strains Lac3 and Lac6 and their presence in strain Lac15. With respect to SRB from other genera, inhibition of the known nitrite reducer Desulfobulbus propionicus by strain CVO and nitrate was transient, whereas inhibition of Desulfobacterium autotrophicum and Desulfobacter postgatei was long-lasting. The results indicate that inhibition of SRB by NR-SOB is caused by nitrite production. Nrf-containing SRB can overcome this inhibition by further reducing nitrite to ammonia, preventing a stalling of the favourable metabolic interactions between these two bacterial groups. Nrf, which is widely distributed in SRB, can thus be regarded as a resistance factor that prevents the inhibition of dissimilatory sulphate reduction by nitrite.200312823193
852960.9644Investigating and Modeling the Regulation of Extracellular Antibiotic Resistance Gene Bioavailability by Naturally Occurring Nanoparticles. Extracellular antibiotic resistance genes (eARGs) are widespread in the environment and can genetically transform bacteria. This work examined the role of environmentally relevant nanoparticles (NPs) in regulating eARG bioavailability. eARGs extracted from antibiotic-resistant B. subtilis were incubated with nonresistant recipient B. subtilis cells. In the mixture, particle type (either humic acid coated nanoparticles (HASNPs) or their micron-sized counterpart (HASPs)), DNase I concentration, and eARG type were systematically varied. Transformants were counted on selective media. Particles decreased bacterial growth and eARG bioavailability in systems without nuclease. When DNase I was present (≥5 μg/mL), particles increased transformation via chromosomal (but not plasmid-borne) eARGs. HASNPs increased transformation more than HASPs, indicating that the smaller nanoparticle with greater surface area per volume is more effective in increasing eARG bioavailability. These results were also modeled via particle aggregation theory, which represented eARG-bacteria interactions as transport leading to collision, followed by attachment. Using attachment efficiency as a fitting factor, the model predicted transformant concentrations within 35% of experimental data. These results confirm the ability of NPs to increase eARG bioavailability and suggest that particle aggregation theory may be a simplified and suitable framework to broadly predict eARG uptake.202235853206
859570.9642Antimicrobial poly(ionic liquid)-induced bacterial nanotube formation and drug-resistance spread. Bacterial nanotubes are tubular membranous structures bulging from the cell surface that can connect neighboring bacteria for the exchange of intercellular substances. However, little is known about the formation and function of bacterial nanotubes under the stress of antimicrobial materials. Herein, an imidazolium-type cationic poly(ionic liquid) (PIL) and corresponding PIL membranes with antimicrobial properties were synthesized. The effects of these cationic polymers on the formation of bacterial nanotubes between Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) or Vibrio fischeri (V. fischeri), followed by intraspecies and interspecies exchange of antibiotic resistance genes (ARGs) were investigated. The results showed that bacteria tend to produce more nanotubes accompanied by drug-resistance trade, which can even make the ARGs of pathogens spread to the environmental microbes of V. fischeri. Given the unique antimicrobial sustainability toward bacteria after they acquire ARGs via bacterial nanotubes, antimicrobial PILs demonstrate bright prospects in the battle against resistant bacteria.202236155673
50880.9642Insights into the chaotropic tolerance of the desert cyanobacterium Chroococcidiopsis sp. 029 (Chroococcidiopsales, Cyanobacteria). The mechanism of perchlorate resistance of the desert cyanobacterium Chroococcidiopsis sp. CCMEE 029 was investigated by assessing whether the pathways associated with its desiccation tolerance might play a role against the destabilizing effects of this chaotropic agent. During 3 weeks of growth in the presence of 2.4 mM perchlorate, an upregulation of trehalose and sucrose biosynthetic pathways was detected. This suggested that in response to the water stress triggered by perchlorate salts, these two compatible solutes play a role in the stabilization of macromolecules and membranes as they do in response to dehydration. During the perchlorate exposure, the production of oxidizing species was observed by using an oxidant-sensing fluorochrome and determining the expression of the antioxidant defense genes, namely superoxide dismutases and catalases, while the presence of oxidative DNA damage was highlighted by the over-expression of genes of the base excision repair. The involvement of desiccation-tolerance mechanisms in the perchlorate resistance of this desert cyanobacterium is interesting since, so far, chaotropic-tolerant bacteria have been identified among halophiles. Hence, it is anticipated that desert microorganisms might possess an unrevealed capability of adapting to perchlorate concentrations exceeding those naturally occurring in dry environments. Furthermore, in the endeavor of supporting future human outposts on Mars, the identified mechanisms might contribute to enhance the perchlorate resistance of microorganisms relevant for biologically driven utilization of the perchlorate-rich soil of the red planet.202438156502
636390.9641The effect of tetronasin and monensin on fermentation, microbial numbers and the development of ionophore-resistant bacteria in the rumen. The Gram-negative rumen bacteria Fibrobacter succinogenes S85, Prevotella ruminicola M384 and Veillonella parvula L59 were grown in media containing successively increasing concentrations of the ionophores, monensin and tetronasin. All three species became more resistant to the ionophore with which they were grown. Increased resistance to one ionophore caused increased resistance to the other, and cross-resistance to another ionophore--lasalocid--and an antibiotic--avoparcin. Recovery of tetronasin-resistant bacteria from the rumen of monensin-fed sheep increased and vice versa, indicating that similar cross-resistance occurred in vivo.19938407673
555100.9641Mutations in dsbA and dsbB, but not dsbC, lead to an enhanced sensitivity of Escherichia coli to Hg2+ and Cd2+. The Dsb proteins are involved in disulfide bond formation, reduction and isomerisation in a number of Gram-negative bacteria. Mutations in dsbA or dsbB, but not dsbC, increase the proportion of proteins with free thiols in the periplasm compared to wild-type. We investigated the effects of mutations in these genes on the bacterial resistance to mercuric and cadmium salts. Mutations in genes involved primarily in disulfide formation (dsbA and dsbB) generally enhanced the sensitivity to Hg2+ and Cd2+ while a mutation of the dsbC gene (primarily an isomerase of disulfide bonds) had no effect. Mutations of the dsb genes had no effect on the expression of the mercury-resistance determinants of the transposon Tn501.199910234837
5070110.9640Sequence-specific DNA solid-phase extraction in an on-chip monolith: Towards detection of antibiotic resistance genes. Antibiotic resistance of bacteria is a growing problem and presents a challenge for prompt treatment in patients with sepsis. Currently used methods rely on culturing or amplification; however, these steps are either time consuming or suffer from interference issues. A microfluidic device was made from black polypropylene, with a monolithic column modified with a capture oligonucleotide for sequence selective solid-phase extraction of a complementary target from a lysate sample. Porous properties of the monolith allow flow and hybridization of a target complementary to the probe immobilized on the column surface. Good flow-through properties enable extraction of a 100μL sample and elution of target DNA in 12min total time. Using a fluorescently labeled target oligonucleotide related to Verona Integron-Mediated Metallo-β-lactamase it was possible to extract and detect a 1pM sample with 83% recovery. Temperature-mediated elution by heating above the duplex melting point provides a clean extract without any agents that interfere with base pairing, allowing various labeling methods or further downstream processing of the eluent. Further integration of this extraction module with a system for isolation and lysis of bacteria from blood, as well as combining with single-molecule detection should allow rapid determination of antibiotic resistance.201728734608
9088120.9639Cocrystallizing and Codelivering Complementary Drugs to Multidrugresistant Tuberculosis Bacteria in Perfecting Multidrug Therapy. Bacteria cells exhibit multidrug resistance in one of two ways: by raising the genetic expression of multidrug efflux pumps or by accumulating several drug-resistant components in many genes. Multidrug-resistive tuberculosis bacteria are treated by multidrug therapy, where a few certain antibacterial drugs are administered together to kill a bacterium jointly. A major drawback of conventional multidrug therapy is that the administration never ensures the reaching of different drug molecules to a particular bacterium cell at the same time, which promotes growing drug resistivity step-wise. As a result, it enhances the treatment time. With additional tabletability and plasticity, the formation of a cocrystal of multidrug can ensure administrating the multidrug chemically together to a target bacterium cell. With properly maintaining the basic philosophy of multidrug therapy here, the synergistic effects of drug molecules can ensure killing the bacteria, even before getting the option to raise the drug resistance against them. This can minimize the treatment span, expenditure and drug resistance. A potential threat of epidemic from tuberculosis has appeared after the Covid-19 outbreak. An unwanted loop of finding molecules with the potential to kill tuberculosis, getting their corresponding drug approvals, and abandoning the drug after facing drug resistance can be suppressed here. This perspective aims to develop the universal drug regimen by postulating the principles of drug molecule selection, cocrystallization, and subsequent harmonisation within a short period to address multidrug-resistant bacteria.202337150990
9365130.9639Hypermutability 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
9412140.9639Persistence: a copacetic and parsimonious hypothesis for the existence of non-inherited resistance to antibiotics. We postulate that phenotypic resistance to antibiotics, persistence, is not an evolved (selected-for) character but rather like mutation, an inadvertent product of different kinds of errors and glitches. The rate of generation of these errors is augmented by exposure to these drugs. The genes that have been identified as contributing to the production of persisters are analogous to the so-called mutator genes; they modulate the rate at which these errors occur and/or are corrected. In theory, these phenotypically resistant bacteria can retard the rate of microbiological cure by antibiotic treatment.201425090240
6788150.9639Release and Constancy of an Antibiotic Resistance Gene in Seawater under Grazing Stress by Ciliates and Heterotrophic Nanoflagellates. Extracellular DNA (exDNA) is released from bacterial cells through various processes. The antibiotic resistance genes (ARGs) coded on exDNA may be horizontally transferred among bacterial communities by natural transformation. We quantitated the released/leaked tetracycline resistance gene, tet(M) over time under grazing stress by ciliates and heterotrophic nanoflagellates (HNFs), and found that extracellular tet(M) (ex-tetM) increased with bacterial grazing. Separate microcosms containing tet(M)-possessing bacteria with ciliates or HNFs were prepared. The copy number of ex-tetM in seawater in the ciliate microcosm rapidly increased until 3 d after the incubation, whereas that in the HNF microcosm showed a slower increase until 20 d. The copy number of ex-tetM was stable in both cases throughout the incubation period, suggesting that extracellular ARGs are preserved in the environment, even in the presence of grazers. Additionally, ARGs in bacterial cells were constant in the presence of grazers. These results suggest that ARGs are not rapidly extinguished in a marine environment under grazing stress.201728592722
9330160.9639Pneumococcal Extracellular Vesicles Mediate Horizontal Gene Transfer via the Transformation Machinery. Bacterial cells secrete extracellular vesicles (EVs), the function of which is a matter of intense investigation. Here, we show that the EVs secreted by the human pathogen Streptococcus pneumoniae (pneumococcus) are associated with bacterial DNA on their surface and can deliver this DNA to the transformation machinery of competent cells. These findings suggest that EVs contribute to gene transfer in Gram-positive bacteria, and in doing so, may promote the spread of drug resistance genes in the population.202338168155
340170.9638Study of MFD-type repair in locus determining resistance of Escherichia coli to streptomycin. The yield of induced mutations to streptomycin resistance (Str) in E. coli, UV-irradiated and temporarily incubated in liquid medium not permitting protein synthesis, depends upon the conditions of preirradiation growth and preirradiation treatment of the bacteria, i.e. on their physiological state at the moment of irradiation. This fact is not readily reconciled with a model postulating mutation production in the structural genes of E. coli during excision repair. A preferred explanation is offered, based on the assumption that the efficiency of mutagenesis at the rpsL (strA) locus is determined by interference of antimutagenic (generalized excision repair and MFD) and promutagenic (mutation fixation of excision repair) events. The participation of macromolecular syntheses in Str mutation fixation is suggested.19863537780
9108180.9638Learning from losers. Bacteria can overcome environmental challenges by killing nearby bacteria and incorporating their DNA.201729148975
8621190.9638Effects of symbiotic bacteria on chemical sensitivity of Daphnia magna. The crustacean zooplankton Daphnia magna has been widely used for chemical toxicity tests. Although abiotic factors have been well documented in ecotoxicological test protocols, biotic factors that may affect the sensitivity to chemical compounds remain limited. Recently, we identified symbiotic bacteria that are critical for the growth and reproduction of D. magna. The presence of symbiotic bacteria on Daphnia raised the question as to whether these bacteria have a positive or negative effect on toxicity tests. In order to evaluate the effects of symbiotic bacteria on toxicity tests, bacteria-free Daphnia were prepared, and their chemical sensitivities were compared with that of Daphnia with symbiotic bacteria based on an acute immobilization test. The Daphnia with symbiotic bacteria showed higher chemical resistance to nonylphenol, fenoxycarb, and pentachlorophenol than bacteria-free Daphnia. These results suggested potential roles of symbiotic bacteria in the chemical resistance of its host Daphnia.201728292585