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The world is facing a significant increase in infections caused by drug-resistant infectious agents. In response, various strategies have been recently explored to treat them, including the development of bacteriocins. Bacteriocins are a group of antimicrobial peptides produced by bacteria, capable of controlling clinically relevant susceptible and drug-resistant bacteria. Bacteriocins have been studied to be able to modify and improve their physicochemical properties, pharmacological effects, and biosafety. This manuscript focuses on the research being developed on the biosafety of bacteriocins, which is a topic that has not been addressed extensively in previous reviews. This work discusses the studies that have tested the effect of bacteriocins against pathogens and assess their toxicity using in vivo models, including murine and other alternative animal models. Thus, this work concludes the urgency to increase and advance the in vivo models that both assess the efficacy of bacteriocins as antimicrobial agents and evaluate possible toxicity and side effects, which are key factors to determine their success as potential therapeutic agents in the fight against infections caused by multidrug-resistant microorganisms.Yunnan Province, China is thought to be the original source of biovar Orientalis of Yersinia pestis, the causative agent of the third plague pandemic that has spread globally since the end of the 19th century. Although encompassing a large area of natural plague foci, Y. pestis strains have rarely been found in live rodents during surveillance in Yunnan, and most isolates are from rodent corpses and their fleas. In 2017, 10 Y. pestis strains were isolated from seven live rodents and three fleas in Heqing County of Yunnan. These strains were supposed to have low virulence to local rodents Eothenomys miletus and Apodemus chevrieri because the rodents were healthy and no dead animals were found in surrounding areas, as had occurred in previous epizootic disease. We performed microscopic and biochemical examinations of the isolates, and compared their whole-genome sequences and transcriptome with those of 10 high virulence Y. pestis strains that were isolated from nine rodents and one parasitic flea in adjacent city (Lijiang). We analyzed the phenotypic, genomic, and transcriptomic characteristics of live rodent isolates. The isolates formed a previously undefined monophyletic branch of Y. pestis that was named 1.IN5. Six SNPs, two indels, and one copy number variation were detected between live rodent isolates and the high virulence neighbors. learn more No obvious functional consequence of these variations was found according to the known annotation information. Among genes which expression differential in the live rodent isolates compared to their high virulent neighbors, we found five iron transfer related ones that were significant up-regulated (| log2 (FC) | > 1, p.adjust less then 0.05), indicating these genes may be related to the low-virulence phenotype. The novel genotype of Y. pestis reported here provides further insights into the evolution and spread of plague as well as clues that may help to decipher the virulence mechanism of this notorious pathogen.Listeria monocytogenes is an intracellular pathogen that is well known for its adaptability to life in a broad spectrum of different niches. RNA-mediated regulatory mechanisms in L. monocytogenes play important roles in successful adaptation providing fast and versatile responses to a changing environment. Recent findings indicate that non-coding RNAs (ncRNAs) regulate a variety of processes in this bacterium, such as environmental sensing, metabolism and virulence, as well as immune responses in eukaryotic cells. In this review, the current knowledge on RNA-mediated regulation in L. monocytogenes is presented, with special focus on the roles and mechanisms underlying modulation of metabolism and virulence. Collectively, these findings point to ncRNAs as important gene regulatory elements in L. monocytogenes, both outside and inside an infected host. However, the involvement of regulatory ncRNAs in bacterial physiology and virulence is still underestimated and probably will be better assessed in the coming years, especially in relation to discovering the regulatory functions of 5' and 3' untranslated regions and excludons, and by exploring the role of ncRNAs in interaction with both bacterial and host proteins.Chagas disease, which is caused by Trypanosoma cruzi, establishes lifelong infections in humans and other mammals that lead to severe cardiac and gastrointestinal complications despite the competent immune response of the hosts. Furthermore, it is a neglected disease that affects 8 million people worldwide. The scenario is even more frustrating since the main chemotherapy is based on benznidazole, a drug that presents severe side effects and low efficacy in the chronic phase of the disease. Thus, the search for new therapeutic alternatives is urgent. In the present study, we investigated the activity of a novel phenyl-tert-butyl-nitrone (PBN) derivate, LQB303, against T. cruzi. LQB303 presented trypanocidal effect against intracellular [IC50/48 h = 2.6 μM] and extracellular amastigotes [IC50/24 h = 3.3 μM] in vitro, leading to parasite lysis; however, it does not present any toxicity to host cells. Despite emerging evidence that mitochondrial metabolism is essential for amastigotes to grow inside mammalian ceficant reduction of the ΔΨm of treated amastigotes. LQB303 had no significant influence on the OCR of treated mammalian cells, evidencing its specificity against T. cruzi mitochondrial metabolism. Our results suggest a promising trypanocidal activity of LQB303, associated with parasite bioenergetic inefficiency, with no influence on the host energy metabolism, a fact that may point to an attractive alternative therapy for Chagas disease.Anaerobic methane oxidizing archaea (ANME) mediate anaerobic oxidation of methane (AOM) in marine sediments and are therefore important for controlling atmospheric methane concentrations in the water column and ultimately the atmosphere. Numerous previous studies have revealed that AOM is coupled to the reduction of different electron acceptors such as sulfate, nitrate/nitrite or Fe(III)/Mn(IV). However, the influence of electron acceptor availability on the in situ ANME community composition in sediments remains largely unknown. Here, we investigated the electron acceptor availability and compared the microbial in situ communities of three methane-rich locations offshore the sub-Antarctic island South Georgia, by Illumina sequencing and qPCR of mcrA genes. link2 The methanic zone (MZ) sediments of Royal Trough and Church Trough comprised high sulfide concentrations of up to 4 and 19 mM, respectively. In contrast, those of the Cumberland Bay fjord accounted for relatively high concentrations of dissolved iron (up to 186 μM). Whereas the ANME community in the sulfidic sites Church Trough and Royal Trough mainly comprised members of the ANME-1 clade, the order-level clade "ANME-1-related" (Lever and Teske, 2015) was most abundant in the iron-rich site in Cumberland Bay fjord, indicating that the availability of electron acceptors has a strong selective effect on the ANME community. This study shows that potential electron acceptors for methane oxidation may serve as environmental filters to select for the ANME community composition and adds to a better understanding of the global importance of AOM.Streptomyces lividans TK24 is a relevant Gram-positive soil inhabiting bacterium and one of the model organisms of the genus Streptomyces. It is known for its potential to produce secondary metabolites, antibiotics, and other industrially relevant products. S. lividans TK24 is the plasmid-free derivative of S. lividans 66 and a close genetic relative of the strain Streptomyces coelicolor A3(2). In this study, we used transcriptome and proteome data to improve the annotation of the S. lividans TK24 genome. The RNA-seq data of primary 5'-ends of transcripts were used to determine transcription start sites (TSS) in the genome. We identified 5,424 TSS, of which 4,664 were assigned to annotated CDS and ncRNAs, 687 to antisense transcripts distributed between 606 CDS and their UTRs, 67 to tRNAs, and 108 to novel transcripts and CDS. Using the TSS data, the promoter regions and their motifs were analyzed in detail, revealing a conserved -10 (TAnnnT) and a weakly conserved -35 region (nTGACn). The analysis of the 5' usage as a secondary metabolite producing strain.Klebsiella variicola is mainly associated with opportunistic infections and frequently identified as Klebsiella pneumoniae. This misidentification implies a wrong epidemiology result as well as incorrect attribution to K. pneumoniae as the etiology of some severe infections. Recently, huge efforts have been made to study K. variicola, however, the biological aspects of this species are still unclear. Here we characterized five K. variicola strains initially identified as K. pneumoniae, with a Vitek-2 System and 16S rRNA sequencing. One-step multiplex polymerase chain reaction and Whole Genome Sequencing (WGS) identified them as K. variicola. Additionally, WGS analysis showed that all the strains are closely related with K. variicola genomes, forming a clustered group, apart from K. pneumoniae and K. quasipneumoniae. Multilocus sequence typing analysis showed four different sequence types (STs) among the strains and for two of them (Kv97 and Kv104) the same ST was assigned. link3 All strains were multidrug-resistant (MDR) and three showed virulence phenotypes including invasion capacity to epithelial cells, and survival in human blood and serum. These results showed the emergence of new K. variicola clones with pathogenic potential to colonize and cause infection in different tissues. These characteristics associated with MDR strains raise great concern for human health.Phytophthora infestans, one of most famous pathogenic oomycetes, triggered the Great Irish Famine from 1845 to 1852. The target of rapamycin (TOR) is well known as a key gene in eukaryotes that controls cell growth, survival and development. However, it is unclear about its function in controlling the mycelial growth, sporulation capacity, spore germination and virulence of Phytophthora infestans. In this study, key components of the TOR signaling pathway are analyzed in detail. TOR inhibitors, including rapamycin (RAP), AZD8055 (AZD), KU-0063794 (KU), and Torin1, inhibit the mycelial growth, sporulation capacity, spore germination, and virulence of Phytophthora infestans with AZD showing the best inhibitory effects on Phytophthora infestans. Importantly, compared with a combination of RAP + KU or RAP + Torin1, the co-application of RAP and AZD show the best synergistic inhibitory effects on P. infestans, resulting in the reduced dosage and increased efficacy of drugs. Transcriptome analysis supports the synergistic effects of the combination of RAP and AZD on gene expression, functions and pathways related to the TOR signaling pathway. Thus, TOR is an important target for controlling Phytophthora infestans, and synergism based on the application of TOR inhibitors exhibit the potential for controlling the growth of Phytophthora infestans.