Mitomycin C as an Anti-Persister Strategy against Toxicity and Synergy Studies.

The combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the lytic phage vB_KpnM-VAC13 in vitro and its safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype.

Therapeutic Importance of Exercise in Neuroplasticity in Adults with Neurological Pathology: Systematic Review.

Neuroplasticity is an essential mechanism by which the nervous system shapes and adapts according to functional requirements. Evidence suggests that physical exercise induces a cascade of cellular processes that favours brain plasticity. The Brain Derived Neurotrophic Factor (BDNF) is a neurotrophin closely linked to neuroplasticity that can be increased due to exercise.

Simultaneous clonal spread of NDM-1-producing ST773 from Ukrainian patients in the Netherlands and Spain.

Objectives: We describe the clonal spread of New Delhi metallo-β-lactamase (NDM) 1-producing isolates belonging to the ST773 clone in Spain and the Netherlands, associated with the transfer of Ukrainian patients during the war.

Methods: Between March and December 2022, nine NDM-1-producing ST773 isolates were recovered from nine Ukrainian patients evacuated to two Spanish ( = 3) and five Dutch ( = 6) hospitals. Antimicrobial susceptibility testing was studied (Sensititre, Microscan, EUCAST-2023).

Phages produce persisters.

Arguably, the greatest threat to bacteria is phages. It is often assumed that those bacteria that escape phage infection have mutated or utilized phage-defence systems; however, another possibility is that a subpopulation forms the dormant persister state in a manner similar to that demonstrated for bacterial cells undergoing nutritive, oxidative, and antibiotic stress. Persister cells do not undergo mutation and survive lethal conditions by ceasing growth transiently.

Regulation of anti-phage defense mechanisms by using cinnamaldehyde as a quorum sensing inhibitor.

Background: Multidrug-resistant bacteria and the shortage of new antibiotics constitute a serious health problem. This problem has led to increased interest in the use of bacteriophages, which have great potential as antimicrobial agents but also carry the risk of inducing resistance. The objective of the present study was to minimize the development of phage resistance in strains by inhibiting quorum sensing (QS) and thus demonstrate the role of QS in regulating defense mechanisms.

Improving phage therapy by evasion of phage resistance mechanisms.

Antibiotic failure is one of the most worrisome threats to global health. Among the new therapeutic efforts that are being explored, the use of bacteriophages (viruses that kill bacteria), also known as 'phages', is being extensively studied as a strategy to target bacterial pathogens. However, one of the main drawbacks of phage therapy is the plethora of defence mechanisms that bacteria use to defend themselves against phages.

Resistance against two lytic phage variants attenuates virulence and antibiotic resistance in .

Background: Bacteriophage therapy is becoming part of mainstream Western medicine since antibiotics of clinical use tend to fail. It involves applying lytic bacteriophages that self-replicate and induce cell lysis, thus killing their hosts. Nevertheless, bacterial killing promotes the selection of resistant clones which sometimes may exhibit a decrease in bacterial virulence or antibiotic resistance.

Single-cell analysis reveals that cryptic prophage protease LfgB protects during oxidative stress by cleaving antitoxin MqsA.

Although toxin/antitoxin (TA) systems are ubiquitous, beyond phage inhibition and mobile element stabilization, their role in host metabolism is obscure. One of the best-characterized TA systems is MqsR/MqsA of , which has been linked previously to protecting gastrointestinal species during the stress it encounters from the bile salt deoxycholate as it colonizes humans. However, some recent whole-population studies have challenged the role of toxins such as MqsR in bacterial physiology since the locus is induced over a hundred-fold during stress, but a phenotype was not found upon its deletion.

Use of Galleria mellonella as an Animal Model for Studying the Antimicrobial Activity of Bacteriophages with Potential Use in Phage Therapy.

Interest in phage therapy has increased in the last decade, and animal models have become essential in this field. The larval stage of the wax moth, Galleria mellonella, represents an easy-to-handle model. The larvae have an innate immune response and survive at 37 °C, which is ideal for infection and antimicrobial studies with bacteriophages.

Molecular studies of phages- in mucoid environment: innovative use of mucolytic agents prior to the administration of lytic phages.

Mucins are important glycoproteins that form a protective layer throughout the gastrointestinal and respiratory tracts. There is scientific evidence of increase in phage-resistance in the presence of mucin for some bacterial pathogens. Manipulation in mucin composition may ultimately influence the effectiveness of phage therapy.

Ribosome inactivation by GTPase RsgA inhibits T4 phage.

Introduction: Bacteria must combat phages, and myriad bacterial anti-phage systems have been discovered that reduce host metabolism, for example, by depleting energetic compounds like ATP and NAD. Hence, these systems indirectly inhibit protein production. Surprisingly, direct reduction of ribosome activity has not been demonstrated to thwart phage.

Appearance of aseptic vascular grafts after endovascular aortic repair on [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography.

Background: Diagnosis of prosthetic vascular graft infection with [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) allows for early detection of functional changes associated with infection, based on increased glucose utilization by activated macrophages and granulocytes. Aseptic vascular grafts, like all foreign bodies, can stimulate an inflammatory response, which can present as increased activity on 18F-FDG PET/CT. Consequently, distinguishing aseptic inflammation from graft infection, though important, can be difficult.

CRISPR-Cas13a-Based Assay for Accurate Detection of OXA-48 and GES Carbapenemases.

Carbapenem-resistant pathogens have been recognized as a health concern as they are both difficult to treat and detect in clinical microbiology laboratories. Researchers are making great efforts to develop highly specific, sensitive, accurate, and rapid diagnostic techniques, required to prevent the spread of these microorganisms and improve the prognosis of patients. In this context, CRISPR-Cas systems are proposed as promising tools for the development of diagnostic methods due to their high specificity; the Cas13a endonuclease can discriminate single nucleotide changes and displays collateral cleavage activity against single-stranded RNA molecules when activated.

Prophage identification and molecular analysis in the genomes of strains isolated from critical care patients.

Prophages are bacteriophages integrated into the bacterial host's chromosome. This research aims to analyze and characterize the existing prophages within a collection of 53 strains from intensive care units (ICUs) in Portugal and Spain. A total of 113 prophages were localized in the collection, with 18 of them being present in more than one strain simultaneously.

Case report: Analysis of phage therapy failure in a patient with a prosthetic vascular graft infection.

Clinical case of a patient with a multidrug-resistant prosthetic vascular graft infection which was treated with a cocktail of phages (PT07, 14/01, and PNM) in combination with ceftazidime-avibactam (CZA). After the application of the phage treatment and in absence of antimicrobial therapy, a new bloodstream infection (BSI) with a septic residual limb metastasis occurred, now involving a wild-type strain being susceptible to ß-lactams and quinolones. Clinical strains were analyzed by microbiology and whole genome sequencing techniques.

Proteomic Study of the Interactions between Phages and the Bacterial Host .

Phages and bacteria have acquired resistance mechanisms for protection. In this context, the aims of the present study were to analyze the proteins isolated from 21 novel lytic phages of Klebsiella pneumoniae in search of defense mechanisms against bacteria and also to determine the infective capacity of the phages. A proteomic study was also conducted to investigate the defense mechanisms of two clinical isolates of K.

Study of 32 new phage tail-like bacteriocins (pyocins) from a clinical collection of Pseudomonas aeruginosa and of their potential use as typing markers and antimicrobial agents.

Phage tail-like bacteriocins (PTLBs) are large proteomic structures similar to the tail phages. These structures function in bacterial competition by making pores in the membrane of their competitors. The PTLBs identified in Pseudomonas aeruginosa are known as R-type and F-type pyocins, which have a narrow spectrum of action.

Relationship between physical activity levels of Portuguese physical therapists and mental health during a COVID-19 pandemic: Being active is the key.

Introduction: Physical activity is essential for a healthy life and quality of life, representing a fundamental role in individuals' physical and mental health. Concomitantly, the physical therapist, through the promotion of physical activity and exercise, can improve mental health, an essential factor in the current pandemic, triggering anxiety, fear, and depression crisis.

Objective: To verify physical activity among Portuguese physical therapists and its association with mental health during pandemic times.

Reverse Transcription-Loop-Mediated Isothermal Amplification-CRISPR-Cas13a Technology as a Promising Diagnostic Tool for SARS-CoV-2.

At the end of 2019, a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), caused a pandemic that persists to date and has resulted in more than 6.2 million deaths. In the last couple of years, researchers have made great efforts to develop a diagnostic technique that maintains high levels of sensitivity and specificity, since an accurate and early diagnosis is required to minimize the prevalence of SARS-CoV-2 infection.

Sustainable and Active Program-Development and Application of SAVING Methodology.

The SAVING project aimed to create a sustainable and active aging program to promote the transition to sustainable aging in residential structures for the elderly (RSEs), developing research activities to apply the best strategies and good practices regarding the promotion of an active, healthy, and sustainable aging regarding social, economic, environmental, and pedagogic aspects. All this innovative methodology was built on a living-lab approach applied in one RSE, that was used as a case study. The results showed that the creation of the SAVING Brigade allowed not only increased reflection and mutual learning, but also created better conditions to face uncertainties and obstacles.