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Antibiotics (Basel, Switzerland) May 2024Biofilm-related infections pose significant challenges in neonatal and pediatric care, contributing to increased morbidity and mortality rates. These complex microbial... (Review)
Review
Biofilm-related infections pose significant challenges in neonatal and pediatric care, contributing to increased morbidity and mortality rates. These complex microbial communities, comprising bacteria and fungi, exhibit resilience against antibiotics and host immune responses. Bacterial species such as , , , and commonly form biofilms on medical devices, exacerbating infection risks. Neonates and children, particularly those in intensive care units, are highly susceptible to biofilm-associated infections due to the prolonged use of invasive devices, such as central lines and endotracheal tubes. Enteral feeding tubes, crucial for neonatal nutritional support, also serve as potential sites for biofilm formation, contributing to recurrent microbial contamination. Moreover, species, including , present emerging challenges in neonatal care, with multi-drug resistant strains posing treatment complexities. Current antimicrobial therapies, while important in managing infections, often fall short in eradicating biofilms, necessitating alternative strategies. The aim of this review is to summarize current knowledge regarding antibiofilm strategies in neonates and in children. Novel approaches focusing on biofilm inhibition and dispersal show promise, including surface modifications, matrix-degrading enzymes, and quorum-sensing inhibitors. Prudent use of medical devices and exploration of innovative antibiofilm therapies are imperative in mitigating neonatal and pediatric biofilm infections.
PubMed: 38927176
DOI: 10.3390/antibiotics13060509 -
Antibiotics (Basel, Switzerland) May 2024Antibiotic resistance (AMR) is a major public health concern. Antimicrobial peptides (AMPs) could be an alternative to conventional antibiotics. The purpose of this...
Antibiotic resistance (AMR) is a major public health concern. Antimicrobial peptides (AMPs) could be an alternative to conventional antibiotics. The purpose of this research was to investigate the antimicrobial ability of the synthetic AMPs (i.e., A-11 and AP19) on the most frequently isolated bacteria in boar semen and their effect on extended boar semen quality during storage. We tested the antimicrobial effect of A-11 and AP19 at different concentrations and compared them with gentamicin for inhibiting the growth of E. coli, Pseudomonas aeruginosa and Proteus mirabilis that were isolated from fresh boar semen. In order to evaluate the effect of AMP on semen qualities on days 0, 1, 3, and 5 after storage at 18 °C, seven fresh boar semen samples were collected, diluted with semen extender with antibiotic (i.e., gentamicin at 200 µg/mL, positive control) or without (negative control), and semen extender contained only A-11 or AP19 at different concentrations (i.e., 62.50, 31.25, and 15.625 µg/mL). The total bacterial count was also measured at 0, 24, 36, 48, and 72 h after storage. Comparable to gentamicin, both A-11 and AP19 inhibited the growth of E. coli, Pseudomonas aeruginosa, and Proteus mirabilis at 62.50, 31.25, and 15.625 µg/mL, respectively. Comparing the total bacterial count at 0, 24, 36, 48 and 72 h after storage, the lowest total bacterial concentration was found in the positive control group ( < 0.05), and an inferior total bacterial concentration was found in the treatment groups than in the negative control. On day 1, there is a lower percentage of all sperm parameters in the AP19 group at a concentration of 62.50 µg/mL compared with the other groups. On day 3, the highest percentage of all sperm parameters was found in the positive control and A-11 at a concentration of 31.25 µg/mL compared with the other groups. The AP19 group at 62.5 µg/mL constantly yielded inferior sperm parameters. On day 5, only A-11 at a concentration of 15.625 µg/mL showed a total motility higher than 70%, which is comparable to the positive control. A-11 and AP19 showed antimicrobial activity against , and isolated from boar semen. Considering their effect on semen quality during storage, these antimicrobial peptides are an alternative to conventional antibiotics used in boar semen extenders. Nevertheless, the utilization of these particular antimicrobial peptides relied on the concentration and duration of storage.
PubMed: 38927156
DOI: 10.3390/antibiotics13060489 -
Antibiotics (Basel, Switzerland) May 2024A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their...
A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their anticancer and antimicrobial properties. A molecular docking analysis was conducted on DHFR, utilizing PDB IDs 1U72 and 2W9S, aiming to design anticancer and antimicrobial drugs, respectively. Among all the synthesized derivatives, compound CTh7 demonstrated the highest potency as a DHFR inhibitor, with an IC value of 0.15 μM. Additionally, it exhibited significant cytotoxic properties, with an IC value of 8.53 µM. The molecular docking analysis of the CTh7 compound revealed that it forms strong interactions with key residues of DHFR such as Glu30, Phe34, Tyr121, Ile16, Val115, and Phe31 within the target protein binding site and displayed excellent docking scores and binding energy (-9.9; -70.38 kcal/mol). Additionally, synthesized compounds were screened for antimicrobial properties, revealing significant antimicrobial potential against bacterial strains and moderate effects against fungal strains. Specifically, compound CTh3 exhibited notable antibacterial efficacy against (MIC = 5 µM). Similarly, compound CTh4 demonstrated significant antibacterial activity against both and , with MIC values of 5 µM for each. A docking analysis of the most active antimicrobial compound CTh3 revealed that it forms hydrogen bonds with Thr121 and Asn18, a π-cation bond with Phe92, and a salt bridge with the polar residue Asp27.
PubMed: 38927146
DOI: 10.3390/antibiotics13060479 -
Antibiotics (Basel, Switzerland) May 2024The present study aims to evaluate the antibacterial activity of five commercially available essential oils (EOs), Lavender (LEO), Clove (CEO), Oregano (OEO), Eucalyptus...
Phytochemical Screening and Antibacterial Activity of Commercially Available Essential Oils Combinations with Conventional Antibiotics against Gram-Positive and Gram-Negative Bacteria.
The present study aims to evaluate the antibacterial activity of five commercially available essential oils (EOs), Lavender (LEO), Clove (CEO), Oregano (OEO), Eucalyptus (EEO), and Peppermint (PEO), against the most-known MDR Gram-positive and Gram-negative bacteria- (ATCC 25923), (ATCC 25922), and (ATCC 27853)-alone and in various combinations. Gas Chromatography-Mass Spectrometry (GC-MS) analysis established their complex compositions. Then, their antibacterial activity-expressed as the inhibition zone diameter (IZD) value (mm)-was investigated in vitro by the diffusimetric antibiogram method, using sterile cellulose discs with Ø 6 mm impregnated with 10 µL of sample and sterile borosilicate glass cylinders loaded with 100 µL; the minimum inhibitory concentration (MIC) value (µg/mL) for each EO was calculated from the IZD values (mm) measured after 24 h. The following EO combinations were evaluated: OEO+CEO, CEO+EEO, CEO+PEO, LEO+EEO, and EEO+PEO. Then, the influence of each dual combination on the activity of three conventional antibacterial drugs-Neomycin (NEO), Tetracycline (TET), and Bacitracin (BAC)-was investigated. The most active EOs against and were LEO and OEO (IZD = 40 mm). They were followed by CEO and EEO (IZD = 20-27 mm); PEO exhibited the lowest antibacterial activity (IZD = 15-20 mm). EEO alone showed the highest inhibitory activity on (IZD = 25-35 mm). It was followed by CEO, LEO, and EEO (IZD = 7-11 mm), while PEO proved no antibacterial action against it (IZD = 0 mm). Only one synergic action was recorded (OEO+CEO against ); EEO+PEO revealed partial synergism against and CEO+PEO showed additive behavior against . Two triple associations with TET showed partial synergism against , and the other two (with NEO and TET) evidenced the same behavior against ; all contained EEO+PEO or CEO+PEO. Most combinations reported indifference. However, numerous cases involved antagonism between the constituents included in the double and triple combinations, and the EOs with the strongest antibacterial activities belonged to the highest antagonistic combinations. A consistent statistical analysis supported our results, showing that the EOs with moderate antibacterial activities could generate combinations with higher inhibitory effects based on synergistic or additive interactions.
PubMed: 38927145
DOI: 10.3390/antibiotics13060478 -
Biomolecules Jun 2024Leucine residues are commonly found in the hydrophobic face of antimicrobial peptides (AMPs) and are crucial for membrane permeabilization, leading to the cell death of...
Leucine residues are commonly found in the hydrophobic face of antimicrobial peptides (AMPs) and are crucial for membrane permeabilization, leading to the cell death of invading pathogens. Melittin, which contains four leucine residues, demonstrates broad-spectrum antimicrobial properties but also significant cytotoxicity against mammalian cells. To enhance the cell selectivity of melittin, this study synthesized five analogs by replacing leucine with its structural isomer, 6-aminohexanoic acid. Among these analogs, Mel-LX3 exhibited potent antibacterial activity against both Gram-positive and Gram-negative bacteria. Importantly, Mel-LX3 displayed significantly reduced hemolytic and cytotoxic effects compared to melittin. Mechanistic studies, including membrane depolarization, SYTOX green uptake, FACScan analysis, and inner/outer membrane permeation assays, demonstrated that Mel-LX3 effectively permeabilized bacterial membranes similar to melittin. Notably, Mel-LX3 showed robust antibacterial activity against methicillin-resistant (MRSA) and multidrug-resistant (MDRPA). Furthermore, Mel-LX3 effectively inhibited biofilm formation and eradicated existing biofilms of MDRPA. With its improved selective antimicrobial and antibiofilm activities, Mel-LX3 emerges as a promising candidate for the development of novel antimicrobial agents. We propose that the substitution of leucine with 6-aminohexanoic acid in AMPs represents a significant strategy for combating resistant bacteria.
Topics: Melitten; Biofilms; Pseudomonas aeruginosa; Microbial Sensitivity Tests; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus aureus; Humans; Hemolysis; Aminocaproic Acid; Gram-Negative Bacteria; Animals
PubMed: 38927102
DOI: 10.3390/biom14060699 -
BMC Microbiology Jun 2024The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated...
BACKGROUND
The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated with an increase in mortality and morbidity rates. The aim of this study was to characterize clinical XDR-PA isolates recovered during six months at three different hospitals in Egypt.
RESULTS
Seventy hospital-acquired clinical isolates of P. aeruginosa were classified into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR), according to their antimicrobial resistance profile. In addition, the possession of genes associated with mobile genetic elements and genes encoding antimicrobial resistance determinants among isolates were detected using polymerase chain reaction. As a result, a significant percentage of the isolates (75.7%) were XDR, while 18.5% were MDR, however only 5.7% of the isolates were non-MDR. The phenotypic detection of carbapenemases, extended-spectrum β-lactamases (ESBLs) and metallo β-lactamase (MBL) enzymes showed that 73.6% of XDR-PA isolates were carbapenemases producers, whereas 75.5% and 88.7% of XDR-PA isolates produced ESBLs and MBL respectively. In addition, PCR screening showed that oxa gene was the most frequently detected gene of carbapenemases (91.4%), while aac(6')-lb gene was mostly detected (84.3%) among the screened aminoglycosides-resistance genes. Furthermore, the molecular detection of the colistin resistance gene showed that 12.9% of isolates harbored mcr-1 gene. Concerning mobile genetic element markers (intI, traA, tnp513, and merA), intI was the highest detected gene as it was amplified in 67 isolates (95.7%). Finally, phylogenetic and molecular typing of the isolates via ERIC-PCR analysis revealed 10 different ERIC fingerprints.
CONCLUSION
The present study revealed a high prevalence of XDR-PA in hospital settings which were resistant to a variety of antibiotics due to several mechanisms. In addition, 98% of the XDR-PA clinical isolates contained at least one gene associated with movable genetic elements, which could have aided the evolution of these XDR-PA strains. To reduce spread of drug resistance, judicious use of antimicrobial agents and strict infection control measures are therefore essential.
Topics: Pseudomonas aeruginosa; Humans; Pseudomonas Infections; Drug Resistance, Multiple, Bacterial; Cross Infection; Egypt; beta-Lactamases; Anti-Bacterial Agents; Microbial Sensitivity Tests; Bacterial Proteins; Hospitals; Interspersed Repetitive Sequences; Polymerase Chain Reaction
PubMed: 38926687
DOI: 10.1186/s12866-024-03321-5 -
The British Journal of Ophthalmology Jun 2024To report an epidemiological update of bacterial keratitis (BK) in a tertiary ophthalmology centre over 20 months compared with a previous study on the same timeframe...
AIMS
To report an epidemiological update of bacterial keratitis (BK) in a tertiary ophthalmology centre over 20 months compared with a previous study on the same timeframe from 1998 to 1999.
METHODS
354 patients with BK documented by microbiological corneal scraping or resolutive under antibiotics treatment from January 2020 to September 2021 were analysed retrospectively.
RESULTS
One or several risk factors were found in 95.2% of patients: contact lens wear (45.2%), ocular surface disease (25.0%), systemic disease (21.8%), ocular trauma (11.9%) and ocular surgery (8.8%). The positivity rate of corneal scrapings was 82.5%, with 18.2% polybacterial. One hundred seventy-five (59.9%) bacteria were Gram-negative, and 117 (40.1%) were Gram-positive. The most common bacteria were (32.5%), spp (18.1%) and (8.2%). Final visual acuity (logarithm of the minimum angle of resolution) was associated with age (r=+0.48; p=0.0001), infiltrate size (r=+0.32; p<0.0001), ocular surface disease (r=+0.13; p=0.03), ocular trauma (r=-0.14; p=0.02) and contact lens wear (r=-0.26; p<0.0001). Gram-negative bacteria were responsible for deeper (r=+0.18; p=0.004) and more extensive infiltrates (r=+0.18; p=0.004) in younger patients (r=-0.19; p=0.003). Compared with the previous period, the positivity rate of corneal scrapings and the proportion of Gram-negative bacteria, especially spp, increased. All and spp were sensitive to quinolones, and all were sensitive to both quinolones and methicillin.
CONCLUSION
Contact lens wear remained the leading risk factor. The bacteria distribution was reversed, with a predominance of Gram-negative bacteria and increased spp.
PubMed: 38925906
DOI: 10.1136/bjo-2024-325261 -
European Respiratory Review : An... Apr 2024Neuroimmune recognition and regulation in the respiratory system is a complex and highly coordinated process involving interactions between the nervous and immune... (Review)
Review
Neuroimmune recognition and regulation in the respiratory system is a complex and highly coordinated process involving interactions between the nervous and immune systems to detect and respond to pathogens, pollutants and other potential hazards in the respiratory tract. This interaction helps maintain the health and integrity of the respiratory system. Therefore, understanding the complex interactions between the respiratory nervous system and immune system is critical to maintaining lung health and developing treatments for respiratory diseases. In this review, we summarise the projection distribution of different types of neurons (trigeminal nerve, glossopharyngeal nerve, vagus nerve, spinal dorsal root nerve, sympathetic nerve) in the respiratory tract. We also introduce several types of cells in the respiratory epithelium that closely interact with nerves (pulmonary neuroendocrine cells, brush cells, solitary chemosensory cells and tastebuds). These cells are primarily located at key positions in the respiratory tract, where nerves project to them, forming neuroepithelial recognition units, thus enhancing the ability of neural recognition. Furthermore, we summarise the roles played by these different neurons in sensing or responding to specific pathogens (influenza, severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, human metapneumovirus, herpes viruses, Sendai parainfluenza virus, , , , amoebae), allergens, atmospheric pollutants (smoking, exhaust pollution), and their potential roles in regulating interactions among different pathogens. We also summarise the prospects of bioelectronic medicine as a third therapeutic approach following drugs and surgery, as well as the potential mechanisms of meditation breathing as an adjunct therapy.
Topics: Humans; Animals; Neuroimmunomodulation; Respiratory System; Host-Pathogen Interactions; Respiratory Tract Diseases; Signal Transduction
PubMed: 38925790
DOI: 10.1183/16000617.0008-2024 -
Anais Da Academia Brasileira de Ciencias 2024I. paraguariensis St. Hil. is a south American species of agronomic interest with studies supporting its medicinal properties. As the investigation of active ingredients...
I. paraguariensis St. Hil. is a south American species of agronomic interest with studies supporting its medicinal properties. As the investigation of active ingredients with antimicrobial effect from medicinal plants is a suitable approach to the current antibacterial resistance problem, the aim of the present study was to determine the antibacterial activity of yerba mate ethanolic extracts against carbapenemase-producing gram-negative bacteria (reference strains and clinical isolates). Extracts showed antibacterial activity against Klebsiella pneumoniae ATCC® BAA-2342™ (KPC producing), Providencia rettgeri (NDM producing), Pseudomonas aeruginosa (MBL producing) and P. aeruginosa (VIM producing) at the concentrations tested. The Minimal-Inhibitory-Concentration and Minimal-Bactericidal-Concentration values ranged between 1 and 32 mg.ml-1 for the reference strains, and between 0.125 and 1 mg.ml-1 for the clinical isolates. The MBC/MIC index characterized the extracts as bactericidal. The combinations of commercial antibiotics and extracts showed a synergistic action on the reference strains studied. The lethal concentration 50 obtained using the Artemia salina toxicity assay were higher than 1 mg.ml-1 for all the extracts, indicating a low toxicity. The in vitro activity and low toxicity suggest that ethanolic I. paraguariensis leaf extracts constitute an outstanding source for new antibacterial compounds, and further studies should be carried out to understand their mechanism of action.
Topics: Plant Extracts; Ilex paraguariensis; beta-Lactamases; Microbial Sensitivity Tests; Plant Leaves; Anti-Bacterial Agents; Gram-Negative Bacteria; Bacterial Proteins; Pseudomonas aeruginosa; Animals; Klebsiella pneumoniae
PubMed: 38922267
DOI: 10.1590/0001-3765202420221129 -
Toxins Jun 2024Extensively drug-resistant infections are emerging as a significant threat associated with adverse patient outcomes. Due to this organism's inherent properties of...
Extensively drug-resistant infections are emerging as a significant threat associated with adverse patient outcomes. Due to this organism's inherent properties of developing antibiotic resistance, we sought to investigate alternative strategies such as identifying "high value" antigens for immunotherapy-based purposes. Through extensive database mining, we discovered that numerous Gram-negative bacterial (GNB) genomes, many of which are known multidrug-resistant (MDR) pathogens, including , horizontally acquired the evolutionarily conserved gene encoding Zonula occludens toxin (Zot) with a substantial degree of homology. The toxin's genomic footprint among so many different GNB stresses its evolutionary importance. By employing in silico techniques such as proteomic-based phylogenetic tracing, in conjunction with comparative structural modeling, we discovered a highly conserved intermembrane associated stretch of 70 amino acids shared among all the GNB strains analyzed. The characterization of our newly identified antigen reveals it to be a "high value" vaccine candidate specific for . This newly identified antigen harbors multiple non-overlapping B- and T-cell epitopes exhibiting very high binding affinities and can adopt identical tertiary structures among the least genetically homologous strains. Taken together, using proteomic-driven reverse vaccinology techniques, we identified multiple "high value" vaccine candidates capable of eliciting a polarized immune response against all the genetic variants tested.
Topics: Pseudomonas aeruginosa; Phylogeny; Pseudomonas Infections; Humans; Epitopes, T-Lymphocyte; Pseudomonas Vaccines; Epitopes, B-Lymphocyte
PubMed: 38922165
DOI: 10.3390/toxins16060271