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The prevalence of multidrug-resistant Gram-negative bacteria is a public health concern. Bacteriophages and bacteriophage-derived lytic enzymes have been studied in response to the emergence of multidrug-resistant bacteria. The availability of tRNAs and endolysin toxicity during recombinant protein expression is circumvented by codon optimization and lower expression levels using inducible pET-type plasmids and controlled cultivation conditions, respectively. The use of polyhistidine tags facilitates endolysin purification and alters antimicrobial activity. Outer membrane permeabilizers, such as organic acids, act synergistically with endolysins, but some endolysins permeate the outer membrane of Gram-negative bacteria per se. However, the outer membrane permeation mechanisms of endolysins remain unclear. Other strategies, such as the co-administration of endolysins with polymyxins, silver nanoparticles, and liposomes confer additional outer membrane permeation. Engineered endolysins comprising domains for outer membrane permeation is also a strategy used to overcome the current challenges on the control of multidrug-resistant Gram-negative bacteria. Metagenomics is a new strategy for screening endolysins with interesting antimicrobial properties from uncultured phage genomes. Here, we review the current state of the art on the heterologous expression of endolysin, showing the potential of bacteriophage endolysins in controlling bacterial infections.

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Genomic compaction is an essential characteristic of living organisms. Nucleoid-associated proteins (NAPs) are a group of small proteins that play crucial roles in chromosome architecture and affect DNA replication, transcription, and recombination by imposing topological alterations in genomic DNA, thereby modulating global gene expression. EbfC/YbaB was first described as a DNA-binding protein of Borrelia burgdorferi that regulates the expression of surface lipoproteins with roles in virulence. Further studies indicated that this protein binds specifically and non-specifically to DNA and colocalises with nucleoids in this bacterium. The data showed that this protein binds to DNA as a homodimer, although it can form other organised structures. Crystallography analysis indicated that the protein possesses domains responsible for protein–protein interactions and forms a “tweezer” structure probably involved in DNA binding. Moreover, sequence analysis revealed conserved motifs that may be associated with dimerisation. Structural analysis also showed that the tridimensional structure of EbfC/YbaB is highly conserved within the bacterial domain. The DNA-binding activity was observed in different bacterial species, suggesting that this protein can protect DNA during stress conditions. These findings indicate that EbfC/YbaB is a broadly distributed NAP. Here, we present a review of the existing data on this NAP.

Purpose of Review The COVID-19 pandemic has been responsible for more than 6.3 million deaths worldwide. During the pandemic, the indiscriminate use of antibiotics has increased, contributing to the spread of multidrug-resistant bacteria. In this review, we aim to determine the spread and impact of antibiotic treatments in patients with COVID-19, focusing on underdeveloped and developing countries. Recent Findings Meta-analysis revealed that bacterial co-infections and secondary infections are relatively rare in COVID-19 patients, corresponding to less than 20% of hospitalized patients. Even so, most of these patients have received antibiotic treatments. Summary This review discusses how the COVID-19 pandemic could increase the emergence of multidrug-resistant strains to currently available antibiotics. Initially, we discussed the spread and impact of multidrug resistance of ESKAPE pathogens associated with nosocomial infections and analyzed their risk of secondary infections in patients with COVID-19. Then we highlight three factors related to the spread of resistant bacteria during the current pandemic: overprescription of antibiotics followed by self-medication. Finally, we discussed the lack of availability of diagnostic tests to discriminate the etiologic agent of a disease. All these factors lead to inappropriate use of antibiotics and, therefore, to an increase in the prevalence of resistance, which can have devastating consequences shortly. The data compiled in this study underscore the importance of epidemiological surveillance of hospital isolates to provide new strategies for preventing and controlling infections caused by multidrug-resistant bacteria. In addition, the bibliographic research also highlights the need for an improvement in antibiotic prescribing in the health system.

Significance and Impact of the Study: Salmonella enterica Typhimurium v11218 is a highly attenuated strain optimized to deliver therapeutic gene products to the cytosol of host cells via bacterial expression systems. v11218 has previously been used to design DNA vaccines. However, the application of this strain for the delivery of anti-cancer genes has been less explored. This study is the first to evaluate the delivery a DNA plasmid for the expression of the p53 tumour suppressor gene to bladder cancer cells using S. enterica Typhimurium. v11218 has intrinsic anti-tumour activity and efficiently delivers p53. Thus, v11218 represents an efficient platform for delivering anti-tumour genes for cancer treatment, and the results obtained with v11218p53 + demonstrate its effectiveness in the context of bladder cancer.

La esteatosis no alcohólica es asociada con pronóstico benigno. Sin embargo, puede progresar a fibrosis, aunque no se comprende completamente el comportamiento de los genes que contribuyen a esta progresión. El objetivo de esta investigación fue analizar los indicios tempranos de fibrogénesis en la esteatosis no alcohólica en pacientes obesos frente a no obesos. Se realizó un estudio descriptivo prospectivo que incluyó a pacientes con esteatosis no alcohólica. Estos fueron divididos en dos grupos: obesos y no obesos. Se obtuvo información sociodemográfica, antropométrica y de padecimientos de componentes del síndrome metabólico. Se determinaron parámetros bioquímicos y niveles de expresión de los genes TNF-α, NF-kβ, CYP2E1, TGF-β, OPN, COL4α5 y HGF por RT-PCR. Los resultados muestran diferencias significativas en los niveles de expresión del gen CYP2E1, siendo mayor en pacientes obesos que padecían síndrome metabólico completo. Además, en pacientes no obesos sin componentes del síndrome metabólico se activa TGF-β como participante de vías fibrogénicas, y en pacientes obesos con síndrome metabólico completo el nivel de expresión significativo de CYP2E1 podría indicar una señal de alarma por un posible progreso de la enfermedad. Debe prestarse especial atención y seguimiento de la esteatosis en pacientes obesos.