Dual functional β-peptide polymer-modified resin beads for bacterial killing and endotoxin adsorption

Abstract Background Bacterial infections and endotoxin contaminations are serious problems in the production/manufacture of food, water, drinks, and injections. The development of effective materials to kill bacteria and adsorb endotoxins, particularly those caused by gram-negative bacteria, represents a major step toward improved safety. As synthetic mimic of host defense peptides, β-peptide polymers are not susceptible to bacterial resistance and exhibit potent bacteria-killing abilities upon antibiotic-resistant bacteria. This study investigated the potential of synthetic β-peptide polymer-modified polyacrylate (PA) beads to kill bacteria and remove endotoxin, i.e. lipopolysaccharide (LPS), produced by these bacteria. Results Synthetic β-peptide polymer-modified PA beads displayed strong antimicrobial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus, as well as excellent biocompatibility. In addition, these β-peptide polymer-modified beads removed around 90% of the endotoxins, even at 200 EU/mL of LPS, a very high concentration of LPS. Conclusions β-peptide polymer-modified PA beads are efficient in bacterial killing and endotoxin adsorption. Hence, these modified beads demonstrate the potential application in the production/manufacture of food, water, drinks, and injections.

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Tackling Virulence of Pseudomonas aeruginosa by the Natural Furanone Sotolon

Antibiotics ◽

10.3390/antibiotics10070871 ◽

2021 ◽

Vol 10 (7) ◽

pp. 871

Author(s):

Mohammed F. Aldawsari ◽

El-Sayed Khafagy ◽

Ahmed Al Saqr ◽

Ahmed Alalaiwe ◽

Hisham A. Abbas ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Virulence Factors ◽

Bacterial Infections ◽

Therapeutic Agent ◽

Bacterial Resistance ◽

Inhibitory Concentration ◽

Bacterial Biofilm ◽

Resistant Bacteria ◽

Resistance Development

The bacterial resistance development due to the incessant administration of antibiotics has led to difficulty in their treatment. Natural adjuvant compounds can be co-administered to hinder the pathogenesis of resistant bacteria. Sotolon is the prevailing aromatic compound that gives fenugreek its typical smell. In the current work, the anti-virulence activities of sotolon on Pseudomonas aeruginosa have been evaluated. P. aeruginosa has been treated with sotolon at sub-minimum inhibitory concentration (MIC), and production of biofilm and other virulence factors were assessed. Moreover, the anti-quorum sensing (QS) activity of sotolon was in-silico evaluated by evaluating the affinity of sotolon to bind to QS receptors, and the expression of QS genes was measured in the presence of sotolon sub-MIC. Furthermore, the sotolon in-vivo capability to protect mice against P. aeruginosa was assessed. Significantly, sotolon decreased the production of bacterial biofilm and virulence factors, the expression of QS genes, and protected mice from P. aeruginosa. Conclusively, the plant natural substance sotolon attenuated the pathogenicity of P. aeruginosa, locating it as a plausible potential therapeutic agent for the treatment of its infections. Sotolon can be used in the treatment of bacterial infections as an alternative or adjuvant to antibiotics to combat their high resistance to antibiotics.

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Avoiding ventilator-associated pneumonia: Curcumin-functionalized endotracheal tube and photodynamic action

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2006759117 ◽

2020 ◽

Vol 117 (37) ◽

pp. 22967-22973

Author(s):

Amanda C. Zangirolami ◽

Lucas D. Dias ◽

Kate C. Blanco ◽

Carolina S. Vinagreiro ◽

Natalia M. Inada ◽

...

Keyword(s):

Endotracheal Tube ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Ventilator Associated Pneumonia ◽

Hospital Acquired Infection ◽

Hospital Acquired Infections ◽

Hospitalization Costs ◽

Hospital Acquired

Hospital-acquired infections are a global health problem that threatens patients’ treatment in intensive care units, causing thousands of deaths and a considerable increase in hospitalization costs. The endotracheal tube (ETT) is a medical device placed in the patient’s trachea to assist breathing and delivering oxygen into the lungs. However, bacterial biofilms forming at the surface of the ETT and the development of multidrug-resistant bacteria are considered the primary causes of ventilator-associated pneumonia (VAP), a severe hospital-acquired infection for significant mortality. Under these circumstances, there has been a need to administrate antibiotics together. Although necessary, it has led to a rapid increase in bacterial resistance to antibiotics. Therefore, it becomes necessary to develop alternatives to prevent and combat these bacterial infections. One possibility is to turn the ETT itself into a bactericide. Some examples reported in the literature present drawbacks. To overcome those issues, we have designed a photosensitizer-containing ETT to be used in photodynamic inactivation (PDI) to avoid bacteria biofilm formation and prevent VAP occurrence during tracheal intubation. This work describes ETT’s functionalization with curcumin photosensitizer, as well as its evaluation in PDI against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. A significant photoinactivation (up to 95%) against Gram-negative and Gram-positive bacteria was observed when curcumin-functionalized endotracheal (ETT-curc) was used. These remarkable results demonstrate this strategy’s potential to combat hospital-acquired infections and contribute to fighting antimicrobial resistance.

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Detection of Quorum-Sensing Molecules for Pathogenic Molecules Using Cell-Based and Cell-Free Biosensors

Antibiotics ◽

10.3390/antibiotics9050259 ◽

2020 ◽

Vol 9 (5) ◽

pp. 259 ◽

Cited By ~ 1

Author(s):

Craig Miller ◽

Jordon Gilmore

Keyword(s):

Quorum Sensing ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Genetic Material ◽

Treatment Strategies ◽

Signaling Molecules ◽

Resistant Bacteria ◽

Acute Infections

Since the discovery and subsequent use of penicillin, antibiotics have been used to treat most bacterial infections in the U.S. Over time, the repeated prescription of many antibiotics has given rise to many antibiotic-resistant microbes. A bacterial strain becomes resistant by horizontal gene transfer, where surviving microbes acquire genetic material or DNA fragments from adjacent bacteria that encode for resistance. In order to avoid significant bacterial resistance, novel and target therapeutics are needed. Further advancement of diagnostic technologies could be used to develop novel treatment strategies. The use of biosensors to detect quorum-sensing signaling molecules has the potential to provide timely diagnostic information toward mitigating the multidrug-resistant bacteria epidemic. Resistance and pathogenesis are controlled by quorum-sensing (QS) circuits. QS systems secrete or passively release signaling molecules when the bacterial concentration reaches a certain threshold. Signaling molecules give an early indication of virulence. Detection of these compounds in vitro or in vivo can be used to identify the onset of infection. Whole-cell and cell-free biosensors have been developed to detect quorum-sensing signaling molecules. This review will give an overview of quorum networks in the most common pathogens found in chronic and acute infections. Additionally, the current state of research surrounding the detection of quorum-sensing molecules will be reviewed. Followed by a discussion of future works toward the advancement of technologies to quantify quorum signaling molecules in chronic and acute infections.

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Multidrug-Resistant Acinetobacter baumannii Genetic Characterization and Spread in Lithuania in 2014, 2016, and 2018

Life ◽

10.3390/life11020151 ◽

2021 ◽

Vol 11 (2) ◽

pp. 151

Author(s):

Tatjana Kirtikliene ◽

Aistė Mierauskaitė ◽

Ilona Razmienė ◽

Nomeda Kuisiene

Keyword(s):

Acinetobacter Baumannii ◽

Resistance Genes ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Variable Number Tandem Repeat ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Essential Information ◽

Acinetobacter Spp

Bacterial resistance to antimicrobial agents plays an important role in the treatment of bacterial infections in healthcare institutions. The spread of multidrug-resistant bacteria can occur during inter- and intra-hospital transmissions among patients and hospital personnel. For this reason, more studies must be conducted to understand how resistance occurs in bacteria and how it moves between hospitals by comparing data from different years and looking out for any patterns that might emerge. Multidrug-resistant (MDR) Acinetobacter spp. was studied at 14 healthcare institutions in Lithuania during 2014, 2016, and 2018 using samples from human bloodstream infections. In total, 194 isolates were collected and identified using MALDI-TOF and VITEK2 analyzers as Acinetobacter baumannii group bacteria. After that, the isolates were analyzed for the presence of different resistance genes (20 genes were analyzed) and characterized by using the Rep-PCR and MLVA (multiple-locus variable-number tandem repeat analysis) genotyping methods. The results of the study showed the relatedness of the different Acinetobacter spp. isolates and a possible circulation of resistance genes or profiles during the different years of the study. This study provides essential information, such as variability and diversity of resistance genes, genetic profiling, and clustering of isolates, to better understand the antimicrobial resistance patterns of Acinetobacter spp. These results can be used to strengthen the control of multidrug-resistant infections in healthcare institutions and to prevent potential outbreaks of this pathogen in the future.

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Modeling bacterial resistance to antibiotics: bacterial conjugation and drug effects

Advances in Difference Equations ◽

10.1186/s13662-021-03423-8 ◽

2021 ◽

Vol 2021 (1) ◽

Author(s):

Pirommas Techitnutsarut ◽

Farida Chamchod

Keyword(s):

Bacterial Infections ◽

Bacterial Resistance ◽

Drug Effects ◽

Antibiotic Usage ◽

Resistant Bacteria ◽

Bacterial Conjugation ◽

Plasmid Loss ◽

Successful Probability ◽

Bacterial Fitness ◽

Antibiotic Agents

AbstractAntibiotic resistance is a major burden in many hospital settings as it drastically reduces the successful probability of treating bacterial infections. Generally, resistance is associated with bacterial fitness reduction and selection pressure from antibiotic usage. Here, we investigate the effects of bacterial conjugation, plasmid loss, and drug responses on the population dynamics of sensitive and resistant bacteria by using a mathematical model. Two types of drugs are considered here: antibiotic M that kills only sensitive bacteria and antibiotic N that kills both bacteria. Our results highlight that larger dose and longer dosing interval of antibiotic M may result in the higher prevalence of resistant bacteria while they do the opposite for antibiotic N. When delays in administering initial and second doses are incorporated, the results demonstrate that the delays may lead to the higher prevalence of resistant bacteria when antibiotic M or N is administered with the longer time of bacteria remaining at the lower prevalence of the latter. Our results highlight that switching antibiotic agents during a treatment course and different bacterial strain characteristics result in a significant impact on the prevalence of resistant bacteria.

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Multiple Mechanisms of the Synthesized Antimicrobial Peptide TS against Gram-Negative Bacteria for High Efficacy Antibacterial Action In Vivo

Molecules ◽

10.3390/molecules26010060 ◽

2020 ◽

Vol 26 (1) ◽

pp. 60

Author(s):

Rui Zhang ◽

Xiaobo Fan ◽

Xinglu Jiang ◽

Mingyuan Zou ◽

Han Xiao ◽

...

Keyword(s):

Antimicrobial Peptide ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Divalent Cations ◽

Resistant Bacteria ◽

Antibacterial Drug ◽

Gram Negative Bacteria ◽

Gram Negative

The emergence of drug-resistant bacteria emphasizes the urgent need for novel antibiotics. The antimicrobial peptide TS shows extensive antibacterial activity in vitro and in vivo, especially in gram-negative bacteria; however, its antibacterial mechanism is unclear. Here, we find that TS without hemolytic activity disrupts the integrity of the outer bacterial cell membrane by displacing divalent cations and competitively binding lipopolysaccharides. In addition, the antimicrobial peptide TS can inhibit and kill E. coli by disintegrating the bacteria from within by interacting with bacterial DNA. Thus, antimicrobial peptide TS’s multiple antibacterial mechanisms may not easily induce bacterial resistance, suggesting use as an antibacterial drug to be for combating bacterial infections in the future.

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A Review on Existing Tetracyclines Analogues and Their Pharmacologically Targeted SAR

RADS Journal of Pharmacy and Pharmaceutical Sciences ◽

10.37962/jpps.v8i3.426 ◽

2021 ◽

Vol 8 (3) ◽

Author(s):

Samreen Tanveer ◽

Athar Masood ◽

Kanwal Ashiq ◽

Mehwish Qayyum ◽

Maydda Asif Bajwa ◽

...

Keyword(s):

Bacterial Infections ◽

Bacterial Resistance ◽

Resistant Bacteria ◽

The Novel ◽

Gram Negative ◽

Biological Targets ◽

Current Review ◽

Bacterial Ribosome ◽

30S Subunit ◽

Potential Activity

Background: Tetracyclines belong to a class of broad spectrum antibiotics. Around the globe, they are prescribed to treat various gram negative and gram positive bacterial infections. Once in the cell, they reversibly bind to the receptors which are located on 30S subunit of bacterial ribosome. They act by averting the protein synthesis, in turn, halting the bacterial growth. Aim and Objectives: The aim of current review is to study tetracyclines, identifying potential activity against infections and highlighting the microbial resistance associated with various analogues. Material and Method: The data for this review is collected from various databases including Scopus, PubMed, Springer Link and Google Scholar. To ensure the credibility only indexed articles were used in current study. Result: The outcome of the study has suggested that tetracyclines and number of its analogues show selective bioactivity and strength to the biological targets. Through modification at certain positions, activity of drug is changed substantially. This not only affects therapeutic activity and safety profile but also has influence the bacterial resistance. Conclusion: As antibiotic resistance amongst bacteria is emerging tremendously, demanding more research. It is still needed to synthesize the novel analogues that would be helpful to cure infections caused by the resistant bacteria. Further these analogues can be tagged with radioisotopes that would be helpful for diagnosis and treatment of infectious diseases.

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Review: Lessons Learned From Clinical Trials Using Antimicrobial Peptides (AMPs)

Frontiers in Microbiology ◽

10.3389/fmicb.2021.616979 ◽

2021 ◽

Vol 12 ◽

Author(s):

Gabrielle S. Dijksteel ◽

Magda M. W. Ulrich ◽

Esther Middelkoop ◽

Bouke K. H. L. Boekema

Keyword(s):

Clinical Trials ◽

Antimicrobial Peptides ◽

Bacterial Resistance ◽

Inflammatory Responses ◽

Membrane Surface ◽

Lessons Learned ◽

Resistant Bacteria ◽

Clinical Implementation ◽

Host Defense Peptides ◽

Yeast Fungi

Antimicrobial peptides (AMPs) or host defense peptides protect the host against various pathogens such as yeast, fungi, viruses and bacteria. AMPs also display immunomodulatory properties ranging from the modulation of inflammatory responses to the promotion of wound healing. More interestingly, AMPs cause cell disruption through non-specific interactions with the membrane surface of pathogens. This is most likely responsible for the low or limited emergence of bacterial resistance against many AMPs. Despite the increasing number of antibiotic-resistant bacteria and the potency of novel AMPs to combat such pathogens, only a few AMPs are in clinical use. Therefore, the current review describes (i) the potential of AMPs as alternatives to antibiotics, (ii) the challenges toward clinical implementation of AMPs and (iii) strategies to improve the success rate of AMPs in clinical trials, emphasizing the lessons we could learn from these trials.

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Two Mechanisms of Killing of Pseudomonas aeruginosa by Tobramycin Assessed at Multiple Inocula via Mechanism-Based Modeling

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.04099-14 ◽

2015 ◽

Vol 59 (4) ◽

pp. 2315-2327 ◽

Cited By ~ 47

Author(s):

Jürgen B. Bulitta ◽

Neang S. Ly ◽

Cornelia B. Landersdorfer ◽

Nicholin A. Wanigaratne ◽

Tony Velkov ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Protein Synthesis ◽

Outer Membrane ◽

Bacterial Resistance ◽

Multidrug Resistant ◽

Quantitative Model ◽

Great Promise ◽

Resistant Bacteria ◽

Multidrug Resistant Bacteria ◽

Bacterial Killing

ABSTRACTBacterial resistance is among the most serious threats to human health globally, and many bacterial isolates have emerged that are resistant to all antibiotics in monotherapy. Aminoglycosides are often used in combination therapies against severe infections by multidrug-resistant bacteria. However, models quantifying different antibacterial effects of aminoglycosides are lacking. While the mode of aminoglycoside action on protein synthesis has often been studied, their disruptive action on the outer membrane of Gram-negative bacteria remains poorly characterized. Here, we developed a novel quantitative model for these two mechanisms of aminoglycoside action, phenotypic tolerance at high bacterial densities, and adaptive bacterial resistance in response to an aminoglycoside (tobramycin) against threePseudomonas aeruginosastrains. At low-intermediate tobramycin concentrations (<4 mg/liter), bacterial killing due to the effect on protein synthesis was most important, whereas disruption of the outer membrane was the predominant killing mechanism at higher tobramycin concentrations (≥8 mg/liter). The extent of killing was comparable across all inocula; however, the rate of bacterial killing and growth was substantially lower at the 108.9CFU/ml inoculum than that at the lower inocula. At 1 to 4 mg/liter tobramycin for strain PAO1-RH, there was a 0.5- to 6-h lag time of killing that was modeled via the time to synthesize hypothetical lethal protein(s). Disruption of the outer bacterial membrane by tobramycin may be critical to enhance the target site penetration of antibiotics used in synergistic combinations with aminoglycosides and thereby combat multidrug-resistant bacteria. The two mechanisms of aminoglycoside action and the new quantitative model hold great promise to rationally design novel, synergistic aminoglycoside combination dosage regimens.

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Synthesis of Ribose-Coated Copper-Based Metal–Organic Framework for Enhanced Antibacterial Potential of Chloramphenicol against Multi-Drug Resistant Bacteria

Antibiotics ◽

10.3390/antibiotics10121469 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1469

Author(s):

Haseena ◽

Adnan Khan ◽

Iqra Ghaffar ◽

Roua S. Baty ◽

Mohamed M. Abdel-Daim ◽

...

Keyword(s):

Bacterial Infections ◽

Bacterial Resistance ◽

Metal Organic Framework ◽

Spherical Shape ◽

Resistant Bacteria ◽

Bacterial Strains ◽

E Coli ◽

Drug Candidates ◽

Metal Organic ◽

New Perspective

The rise in bacterial resistance to currently used antibiotics is the main focus of medical researchers. Bacterial multidrug resistance (MDR) is a major threat to humans, as it is linked to greater rates of chronic disease and mortality. Hence, there is an urgent need for developing effective strategies to overcome the bacterial MDR. Metal–organic frameworks (MOFs) are a new class of porous crystalline materials made up of metal ions and organic ligands that can vary their pore size and structure to better encapsulate drug candidates. This study reports the synthesis of ribose-coated Cu-MOFs for enhanced bactericidal activity of chloramphenicol (CHL) against Escherichia coli (resistant and sensitive) and MDR Pseudomonas aeruginosa. The synthesized Cu-MOFs were characterized with DLS, FT-IR, powder X-ray diffraction, scanning electron microscope, and atomic force microscope. They were further investigated for their efficacy against selected bacterial strains. The synthesized ribose-coated Cu-MOFs were observed as spherical shape structure with the particle size of 562.84 ± 13.42 nm. CHL caused the increased inhibition of E. coli and MDR P. aeruginosa with significantly reduced MIC and MBIC values after being encapsulated in ribose-coated Cu-MOFs. The morphological analysis of the bacterial strains treated with ribose-coated CHL-Cu-MOFs showed the complete morphological distortion of both E. coli and MDR P. aeruginosa. Based on the results of the study, it can be suggested that ribose-coated Cu-MOFs may be an effective alternate candidate to overcome the MDR and provide new perspective for the treatment of MDR bacterial infections.

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