scholarly journals Cationic antimicrobial peptides serve as activation signals for the Salmonella Typhimurium PhoPQ and PmrAB regulons in vitro and in vivo

Author(s):  
Susan M. Richards ◽  
Kristi L. Strandberg ◽  
Megan Conroy ◽  
John S. Gunn
2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.


2021 ◽  
Vol 120 (3) ◽  
pp. 74a
Author(s):  
Satoshi Katsube ◽  
Katleen Willibal ◽  
Elena B. Tikhonova ◽  
Hariharan Parameswaran ◽  
Sangama Vemulapally ◽  
...  

1993 ◽  
pp. 427-430
Author(s):  
Mark Sydenham ◽  
Derek Pickard ◽  
Carlos Hormaeche ◽  
Gordon Dougan ◽  
Steven Chatfield

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 76
Author(s):  
Albert Bolatchiev

The antimicrobial peptides human Beta-defensin-3 (hBD-3) and Epinecidin-1 (Epi-1; by Epinephelus coioides) could be a promising tool to develop novel antibacterials to combat antibiotic resistance. The antibacterial activity of Epi-1 + vancomycin against methicillin-resistant Staphylococcus aureus (22 isolates) and Epi-1 + hBD-3 against carbapenem-resistant isolates of Klebsiella pneumoniae (n = 23), Klebsiella aerogenes (n = 17), Acinetobacter baumannii (n = 9), and Pseudomonas aeruginosa (n = 13) was studied in vitro. To evaluate the in vivo efficacy of hBD-3 and Epi-1, ICR (CD-1) mice were injected intraperitoneally with a lethal dose of K. pneumoniae or P. aeruginosa. The animals received a single injection of either sterile saline, hBD-3 monotherapy, meropenem monotherapy, hBD-3 + meropenem, or hBD-3 + Epi-1. Studied peptides showed antibacterial activity in vitro against all studied clinical isolates in a concentration of 2 to 32 mg/L. In both experimental models of murine sepsis, an increase in survival rate was seen with hBD-3 monotherapy, hBD-3 + meropenem, and hBD-3 + Epi-1. For K. pneumoniae-sepsis, hBD-3 was shown to be a promising option in overcoming the resistance of Klebsiella spp. to carbapenems, though more research is needed. In the P. aeruginosa-sepsis model, the addition of Epi-1 to hBD-3 was found to have a slightly reduced mortality rate compared to hBD-3 monotherapy.


eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Mark Austin Hanson ◽  
Anna Dostálová ◽  
Camilla Ceroni ◽  
Mickael Poidevin ◽  
Shu Kondo ◽  
...  

Antimicrobial peptides (AMPs) are host-encoded antibiotics that combat invading microorganisms. These short, cationic peptides have been implicated in many biological processes, primarily involving innate immunity. In vitro studies have shown AMPs kill bacteria and fungi at physiological concentrations, but little validation has been done in vivo. We utilized CRISPR gene editing to delete most known immune-inducible AMPs of Drosophila, namely: 4 Attacins, 2 Diptericins, Drosocin, Drosomycin, Metchnikowin and Defensin. Using individual and multiple knockouts, including flies lacking these ten AMP genes, we characterize the in vivo function of individual and groups of AMPs against diverse bacterial and fungal pathogens. We found that Drosophila AMPs act primarily against Gram-negative bacteria and fungi, contributing either additively or synergistically. We also describe remarkable specificity wherein certain AMPs contribute the bulk of microbicidal activity against specific pathogens, providing functional demonstrations of highly specific AMP-pathogen interactions in an in vivo setting.


2017 ◽  
Vol 83 (4) ◽  
pp. 391-402
Author(s):  
Jhanina Rodríguez Carrasco ◽  
Paula García-Godos Alcázar

La investigación tuvo como objetivos aislar e identificar bacterias lácticas (BAL), evaluar la capacidad probiótica in vitro e in vivo de bacterias lácticas aisladas de chicha de molle, para ello se muestreó chichas de molle elaboradas artesanalmente de las provincias de Huanta y Huamanga, aislando 55 cepas BAL e identificando a Lactobacillus plantarum, Lactobacillus maltaromicus y Leuconostoc mesenteroides en base a la coloración Gram, producción de gas, gluconato y fermentación de azúcares. Para evaluar la capacidad probiótica in vitro se realizaron pruebas de antagonismo entre BAL con cuatro microorganismos patógenos (Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 14028, Staphylococus aureus ATCC 25923 y Candida albicans ATCC 90028), mostrándose que 14 de las 55 cepas BAL producen sustancias inhibitorias de amplio espectro; asimismo, se evaluó la capacidad de tolerancia a condiciones gastrointestinales de cepas BAL, realizando ensayos a diferentes pHs , diferentes concentraciones de sales biliares y extracto gástrico artificial, resultando 25 cepas BAL con capacidad de tolerancia gastrointestinal y se seleccionaron cuatro cepas con mayor diámetro de halos de inhibición y cepas tolerantes a condiciones gastrointestinales siendo las cepas: BL-1 (Lactobacillus plantarum), BL-26 (Lactobacillus maltaromicus), BL-27 (Lactobacillus plantarum) y BL-53 (Lactobacillus maltaromicus), a las cuales se evaluaron la capacidad probiótica in vivo en 20 ratas para luego realizar recuento de BAL en el intestino a los 21 días, encontrándose en el grupo de estudio con BAL a 60x1019 UFC/ mL, mientras en el tratamiento con BAL más yacón a 25x1024 UFC/mL y los tratamientos de yacón y control a 50x1014 UFC/mL de BAL obteniéndose una de ganancia de peso en ratas en el grupo de estudio de BAL más yacón de 46 g, mientras con bacterias lácticas se tuvo 24 g y 16 g en el grupo control y extracto de yacón. En consecuencia esta investigación demuestra que la toma diaria de bebidas fermentadas tradicionales favorece el incremento de Lactobacillus en la microbiota intestinal.


2005 ◽  
Vol 390 (3) ◽  
pp. 769-776 ◽  
Author(s):  
Sarah Sanowar ◽  
Hervé Le Moual

Two-component signal-transduction systems are widespread in bacteria. They are usually composed of a transmembrane histidine kinase sensor and a cytoplasmic response regulator. The PhoP/PhoQ two-component system of Salmonella typhimurium contributes to virulence by co-ordinating the adaptation to low concentrations of environmental Mg2+. Limiting concentrations of extracellular Mg2+ activate the PhoP/PhoQ phosphorylation cascade modulating the transcription of PhoP-regulated genes. In contrast, high concentrations of extracellular Mg2+ stimulate the dephosphorylation of the response regulator PhoP by the PhoQ kinase sensor. In the present study, we report the purification and functional reconstitution of PhoQHis, a PhoQ variant with a C-terminal His tag, into Escherichia coli liposomes. The functionality of PhoQHis was essentially similar to that of PhoQ as shown in vivo and in vitro. Purified PhoQHis was inserted into liposomes in a unidirectional orientation, with the sensory domain facing the lumen and the catalytic domain facing the extraluminal environment. Reconstituted PhoQHis exhibited all the catalytic activities that have been described for histidine kinase sensors. Reconstituted PhoQHis was capable of autokinase activity when incubated in the presence of Mg2+-ATP. The phosphoryl group could be transferred from reconstituted PhoQHis to PhoP. Reconstituted PhoQHis catalysed the dephosphorylation of phospho-PhoP and this activity was stimulated by the addition of extraluminal ADP.


mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Giuseppe Buda De Cesare ◽  
Shane A. Cristy ◽  
Danielle A. Garsin ◽  
Michael C. Lorenz

ABSTRACT Invasive fungal infections in humans are generally associated with high mortality, making the choice of antifungal drug crucial for the outcome of the patient. The limited spectrum of antifungals available and the development of drug resistance represent the main concerns for the current antifungal treatments, requiring alternative strategies. Antimicrobial peptides (AMPs), expressed in several organisms and used as first-line defenses against microbial infections, have emerged as potential candidates for developing new antifungal therapies, characterized by negligible host toxicity and low resistance rates. Most of the current literature focuses on peptides with antibacterial activity, but there are fewer studies of their antifungal properties. This review focuses on AMPs with antifungal effects, including their in vitro and in vivo activities, with the biological repercussions on the fungal cells, when known. The classification of the peptides is based on their mode of action: although the majority of AMPs exert their activity through the interaction with membranes, other mechanisms have been identified, including cell wall inhibition and nucleic acid binding. In addition, antifungal compounds with unknown modes of action are also described. The elucidation of such mechanisms can be useful to identify novel drug targets and, possibly, to serve as the templates for the synthesis of new antimicrobial compounds with increased activity and reduced host toxicity.


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