Spontaneous Emergence of Cefiderocol Resistance in KPC-163: Genomic and Transcriptomic Insights.

Carbapenem-resistant (CRKP) is an urgent public health threat due to its rapid dissemination and resistance to last-line antibiotics. Cefiderocol (FDC), a novel siderophore cephalosporin, targets resistant Gram-negative pathogens by exploiting bacterial iron uptake mechanisms. However, resistance to FDC is emerging among carbapenemase (KPC)-producing strains.

PrtA-mediated flagellar turnover is essential for robust biofilm development in .

Biofilm formation is crucial for bacterial persistence, requiring precise regulatory mechanisms to transition from motility to sessility. Here, we uncover the role of the metalloprotease PrtA in biofilm development and its interaction with flagellar components. Loss of PrtA leads to reduced biofilm biomass, thickness, and viable cell counts, as shown through high-resolution confocal microscopy.

Insights into AMA205's Unprecedented Antibiotic Resistance.

The rise of antibiotic-resistant bacteria in clinical settings has become a significant global concern. Among these bacteria, stands out due to its remarkable ability to acquire resistance genes and persist in hospital environments, leading to some of the most challenging infections. Horizontal gene transfer (HGT) plays a crucial role in the evolution of this pathogen.

Unraveling the role of UilS, a urea-induced acyl-homoserine lactonase that enhances fitness, interbacterial competition, and urinary tract infection.

Unlabelled: , a member of the Enterobacteriaceae family, is an opportunistic human pathogen and a frequent cause of urinary tract infections. Clinical isolates often exhibit resistance to multiple antibiotics, posing challenges for successful treatment. Understanding its pathogenic mechanisms is crucial for elucidating new potential targets to develop effective therapeutic interventions and manage infections.

Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant spp.

Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) infections. While resistance has already been reported in , combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations.

Carbapenem-resistant Acinetobacter baumannii (CRAB): metabolic adaptation and transcriptional response to human urine (HU).

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major human pathogen and a research priority for developing new antimicrobial agents. CRAB is a causative agent of a variety of infections in different body sites. One of the manifestations is catheter-associated urinary tract infection, which exposes the bacteria to the host's urine, creating a particular environment.

Lacticaseibacillus rhamnosus CRL 2244 secreted metabolites display killing and antibiotic synergistic activity against multi-drug resistant pathogens.

A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel therapeutic options, few antibiotics targeting MDR have been approved by the Food and Drug Administration (FDA). Lactic acid bacteria have emerged as a promising therapeutic alternative due to their demonstrated ability to combat MDR pathogens in vitro.

Carbapenem-resistant Acinetobacter baumannii (CRAB): metabolic adaptation and transcriptional response to human urine (HU).

Carbapenem-resistant (CRAB) is a major human pathogen and a research priority for developing new antimicrobial agents. CRAB is a causative agent of a variety of infections in different body sites. One of the manifestations is catheter-associated urinary tract infection, which exposes the bacteria to the host's urine, creating a particular environment.

Antimicrobial activity of the Lacticaseibacillus rhamnosus CRL 2244 and its impact on the phenotypic and transcriptional responses in carbapenem resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a recognized nosocomial pathogen with limited antibiotic treatment options. Lactic acid bacteria (LAB) constitute a promising therapeutic alternative. Here we studied the antibacterial properties of a collection of LAB strains using phenotypic and transcriptomic analysis against A.

ShlA toxin of Serratia induces P2Y2- and α5β1-dependent autophagy and bacterial clearance from host cells.

Serratia marcescens is an opportunistic human pathogen involved in antibiotic-resistant hospital acquired infections. Upon contact with the host epithelial cell and prior to internalization, Serratia induces an early autophagic response that is entirely dependent on the ShlA toxin. Once Serratia invades the eukaryotic cell and multiples inside an intracellular vacuole, ShlA expression also promotes an exocytic event that allows bacterial egress from the host cell without compromising its integrity.

Induced Heteroresistance in Carbapenem-Resistant (CRAB) via Exposure to Human Pleural Fluid (HPF) and Its Impact on Cefiderocol Susceptibility.

Infections caused by Carbapenem-resistant (CRAB) isolates, such as hospital-acquired pneumonia (HAP), bacteremia, and skin and soft tissue infections, among others, are particularly challenging to treat. Cefiderocol, a chlorocatechol-substituted siderophore antibiotic, was approved by the U.S.

Phenotypic and transcriptional analysis of the antimicrobial effect of lactic acid bacteria on carbapenem-resistant Acinetobacter baumannii: Lacticaseibacillus rhamnosus CRL 2244 an alternative strategy to overcome resistance?".

Carbapenem-resistant (CRAB) is a recognized nosocomial pathogen with limited antibiotic treatment options. Lactic acid bacteria (LAB) constitute a promising therapeutic alternative. Here we studied the antibacterial properties of a collection of LAB strains using phenotypic and transcriptomic analysis against clinical strains.

Genomic Comparative Analysis of Two Multi-Drug Resistance (MDR) Clinical Strains Assigned to International Clonal Lineage II Recovered Pre- and Post-COVID-19 Pandemic.

Background: After the emergence of COVID-19, numerous cases of /SARS-CoV-2 co-infection were reported. Whether the co-infecting strains have distinctive characteristics remains unknown.

Methods And Results: AMA_NO was isolated in 2021 from a patient with COVID-19.

The Iron Content of Human Serum Albumin Modulates the Susceptibility of to Cefiderocol.

The mortality rates of patients infected with who were treated with cefiderocol (CFDC) were not as favorable as those receiving the best available treatment for pulmonary and bloodstream infections. Previous studies showed that the presence of human serum albumin (HSA) or HSA-containing fluids, such as human serum (HS) or human pleural fluid (HPF), in the growth medium is correlated with a decrease in the expression of genes associated with high-affinity siderophore-mediated iron uptake systems. These observations may explain the complexities of the observed clinical performance of CFDC in pulmonary and bloodstream infections, because ferric siderophore transporters enhance the penetration of CFDC into the bacterial cell.

Human serum albumin (HSA) regulates the expression of histone-like nucleoid structure protein (H-NS) in Acinetobacter baumannii.

According to the Centers for Disease Control and Prevention, Acinetobacter baumannii is listed among the most threatening pathogens. A. baumannii is mainly a nosocomial pathogen with a distinctive ability to survive in multiple environments.

Acinetobacter baumannii response to cefiderocol challenge in human urine.

Cefiderocol (CFDC) is a novel chlorocatechol-substituted siderophore antibiotic approved to treat complicated urinary tract infections (cUTI) and hospital-acquired and ventilator-acquired pneumonia (HAP/VAP). Previous work determined that albumin-rich human fluids increase the minimum inhibitory concentration (MICs) of Acinetobacter baumannii against CFDC and reduce the expression of genes related to iron uptake systems. This latter effect may contribute to the need for higher concentrations of CFDC to inhibit growth.

α-Toxin Effect on Behavior.

Polymicrobial infections are more challenging to treat and are recognized as responsible for significant morbidity and mortality. It has been demonstrated that multiple Gram-negative organisms take advantage of the effects of α-toxin on mucosal host defense, resulting in proliferation and dissemination of the co-infecting pathogens. Through phenotypic approaches, we observed a decrease in the motility of A118 after exposure to cell-free conditioned media (CFCM) of strains, USA300 and LS1.

Human Serum Proteins and Susceptibility of to Cefiderocol: Role of Iron Transport.

Cefiderocol, a recently introduced antibiotic, has a chemical structure that includes a cephalosporin that targets cell wall synthesis and a chlorocatechol siderophore moiety that facilitates cell penetration by active iron transporters. Analysis of the effect that human serum, human serum albumin, and human pleural fluid had on growing showed that genes related to iron uptake were down-regulated. At the same time, β-lactamase genes were expressed at higher levels.

Involvement of the Histone-Like Nucleoid Structuring Protein (H-NS) in Natural Transformation.

Most strains are naturally competent. Although some information is available about factors that enhance or reduce the frequency of the transformation of this bacterium, the regulatory elements and mechanisms are barely understood. In this article, we describe studies on the role of the histone-like nucleoid structuring protein, H-NS, in the regulation of the expression of genes related to natural competency and the ability to uptake foreign DNA.

Histone-like nucleoid-structuring protein (H-NS) regulatory role in antibiotic resistance in Acinetobacter baumannii.

In the multidrug resistant (MDR) pathogen Acinetobacter baumannii the global repressor H-NS was shown to modulate the expression of genes involved in pathogenesis and stress response. In addition, H-NS inactivation results in an increased resistance to colistin, and in a hypermotile phenotype an altered stress response. To further contribute to the knowledge of this key transcriptional regulator in A.

Effect of Serum Albumin, a Component of Human Pleural Fluid, on Transcriptional and Phenotypic Changes on Acinetobacter baumannii A118.

Acinetobacter baumannii is a multidrug-resistant pathogen that causes numerous infections associated with high mortality rates. Exposure to human body fluids, such as human pleural fluid (HPF) and human serum, modulates gene expression in A. baumannii, leading to changes in its pathogenic behavior.

Interaction of with Human Serum Albumin: Does the Host Determine the Outcome?

has become a serious threat to human health due to its extreme antibiotic resistance, environmental persistence, and capacity to survive within the host. Two strains, A118 and AB5075, commonly used as model systems, and three carbapenem-resistant strains, which are becoming ever more dangerous due to the multiple drugs they can resist, were exposed to 3.5% human serum albumin (HSA) and human serum (HS) to evaluate their response with respect to antimicrobial resistance, biofilm formation, and quorum sensing, all features responsible for increasing survival and persistence in the environment and human body.