Fierce poison to others: the phenomenon of bacterial dependence on antibiotics.

Beyond the development of resistance, the effects of antibiotics on bacteria and microbial communities are complex and far from exhaustively studied. In the context of the current global antimicrobial resistance crisis, understanding the adaptive and physiological responses of bacteria to antimicrobials is of paramount importance along with the development of new therapies. Bacterial dependence on antibiotics is a phenomenon in which antimicrobials instead of eliminating the pathogens actually provide a boost for their growth. This trait comprises an extreme example of the complexities of responses elicited by microorganisms to these drugs. This compelling evolutionary trait was readily described along with the first wave of antibiotics use and dependence to various antimicrobials has been reported. Nevertheless, current molecular characterizations have been focused on dependence on vancomycin, linezolid and colistin, three critically important antibiotics frequently used as last resource therapy for multi resistant pathogens. Outstanding advances have been made in understanding the molecular basis for the dependence to vancomycin, including specific mutations involved. Regarding linezolid and colistin, the general physiological components affected by the dependence, namely ribosomes and membrane function respectively, have been established. Nonetheless the implications of antibiotic dependence in clinically relevant features, such as virulence, epidemics, relationship with development of resistance, diagnostics and therapy effectiveness require clarification. This review presents a brief introduction of the phenomenon of bacterial dependence to antibiotics and a summary on early and current research concerning the basis for this trait. Furthermore, the available information on the effect of dependence in key clinical aspects is discussed. The studies performed so far underline the need to fully disclose the biological and clinical significance of this trait in pathogens to successfully assess its role in resistance and to design adjusted therapies.

Severe coronavirus HCoV-NL63 pneumonia in a patient receiving blinatumomab with secondary antibody deficiency in COVID-19 times.

Introduction: Human coronavirus NL63 (HCoV-NL63) is one of four common human respiratory coronaviruses. It causes lower respiratory tract infections in young children, elderly and immunosuppressed people, which could result in fatal outcomes. In this time of pandemic, we want to highlight the importance of other coronaviruses infection besides SARS-CoV-2, especially in a patient with underlying conditions like acute lymphoblastic leukemia, receiving immunosuppressive therapy that could result in humoral secondary immunodeficiencies. Case report: We present the case of a 44-year-old Colombian man with acute lymphoblastic leukemia who developed HCoV-NL63 pulmonary infection after the first month of treatment with blinatumomab complicated with severe secondary hypogammaglobulinemia. HCoV-NL63 was detected by multiplex PCR, and HCoV-NL63 viral pneumonia was diagnosed. Hypogammaglobulinemia was studied by determining serum immunoglobulins levels and protein electrophoresis. The treatment consisted of supportive therapy and replacement with intravenous immunoglobulins. After therapy, the patient improved his oxygenation, and the infection was resolved in a few days. Conclusions: This case highlights the relevance of other coronaviruses infections besides SARS-CoV-2 in patients receiving immunosuppressive therapy who develop secondary antibody deficiency, and the importance of replacement therapy with intravenous immunoglobulins at early stage of infection with HCoV-NL63.

Identification of Differentially Expressed Genes in Nocardia brasiliensis Induced by Progesterone and Dihydrotestosterone Using Differential Display PCR.

Sex steroid hormones have an important physiological role in humans. They can also affect the gene expression of many organisms, including bacteria. In Mexico, Nocardia brasiliensis is the main causative agent of actinomycetoma, a granulomatous disease more frequent in men than women, which is thought to be related to a higher occupational risk in men. Therefore, it has been suggested that differences in clinical presentation could be related to sex steroid hormone levels. Attempting to explain the differences in actinomycetoma prevalence between men and women, in this work, the effect of progesterone and dihydrotestosterone on the genetic expression of N. brasiliensis was investigated using a differential display polymerase chain reaction assay. The results showed that both hormones affected the expression of genes encoding proteins related to central metabolism and hypothetical proteins with unknown functions. This study also demonstrated the utility of differential display in this modern era and provided a first approach to the effect of sex hormones on N. brasiliensis gene expression.

The Hcp-like protein HilE inhibits homodimerization and DNA binding of the virulence-associated transcriptional regulator HilD in Salmonella.

HilD is an AraC-like transcriptional regulator that plays a central role in Salmonella virulence. HilD controls the expression of the genes within the Salmonella pathogenicity island 1 (SPI-1) and of several genes located outside SPI-1, which are mainly required for Salmonella invasion of host cells. The expression, amount, and activity of HilD are tightly controlled by the activities of several factors. The HilE protein represses the expression of the SPI-1 genes through its interaction with HilD; however, the mechanism by which HilE affects HilD is unknown. In this study, we used genetic and biochemical assays revealing how HilE controls the transcriptional activity of HilD. We found that HilD needs to assemble in homodimers to induce expression of its target genes. Our results further indicated that HilE individually interacts with each the central and the C-terminal HilD regions, mediating dimerization and DNA binding, respectively. We also observed that these interactions consistently inhibit HilD dimerization and DNA binding. Interestingly, a computational analysis revealed that HilE shares sequence and structural similarities with Hcp proteins, which act as structural components of type 6 secretion systems in Gram-negative bacteria. In conclusion, our results uncover the molecular mechanism by which the Hcp-like protein HilE controls dimerization and DNA binding of the virulence-promoting transcriptional regulator HilD. Our findings may indicate that HilE's activity represents a functional adaptation during the evolution of Salmonella pathogenicity.