Designer broad-spectrum polyimidazolium antibiotics

For a myriad of different reasons most antimicrobial peptides (AMPs) have failed to reach clinical application. Different AMPs have different shortcomings including but not limited to toxicity issues, potency, limited spectrum of activity, or reduced activity in situ. We synthesized several cationic peptide mimics, main-chain cationic polyimidazoliums (PIMs), and discovered that, although select PIMs show little acute mammalian cell toxicity, they are potent broad-spectrum antibiotics with activity against even pan-antibiotic-resistant gram-positive and gram-negative bacteria, and mycobacteria. We selected PIM1, a particularly potent PIM, for mechanistic studies. Our experiments indicate PIM1 binds bacterial cell membranes by hydrophobic and electrostatic interactions, enters cells, and ultimately kills bacteria. Unlike cationic AMPs, such as colistin (CST), PIM1 does not permeabilize cell membranes. We show that a membrane electric potential is required for PIM1 activity. In laboratory evolution experiments with the gram-positiveStaphylococcus aureuswe obtained PIM1-resistant isolates most of which had menaquinone mutations, and we found that a site-directed menaquinone mutation also conferred PIM1 resistance. In similar experiments with the gram-negative pathogenPseudomonas aeruginosa,PIM1-resistant mutants did not emerge. Although PIM1 was efficacious as a topical agent, intraperitoneal administration of PIM1 in mice showed some toxicity. We synthesized a PIM1 derivative, PIM1D, which is less hydrophobic than PIM1. PIM1D did not show evidence of toxicity but retained antibacterial activity and showed efficacy in murine sepsis infections. Our evidence indicates the PIMs have potential as candidates for development of new drugs for treatment of pan-resistant bacterial infections.

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Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections

Nanoscale Horizons ◽

10.1039/d0nh00624f ◽

2021 ◽

Author(s):

Byungji Kim ◽

Qinglin Yang ◽

Leslie W. Chan ◽

Sangeeta N. Bhatia ◽

Erkki Ruoslahti ◽

...

Keyword(s):

Porous Silicon ◽

Broad Spectrum ◽

Therapeutic Efficacy ◽

Bacterial Infections ◽

Silicon Nanoparticles ◽

First Line ◽

Gram Positive ◽

Gram Negative ◽

Porous Silicon Nanoparticles

RNAi-mediated immunotherapy provided by fusogenic porous silicon nanoparticles demonstrates superior therapeutic efficacy against both Gram-positive and Gram-negative bacterial infections compared with first-line antibiotics.

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Antibacterial Potential of Aloe weloensis (Aloeacea) Leaf Latex against Gram-Positive and Gram-Negative Bacteria Strains

International Journal of Microbiology ◽

10.1155/2019/5328238 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4

Author(s):

Yohannes Kelifa Emiru ◽

Ebrahim Abdela Siraj ◽

Tekleab Teka Teklehaimanot ◽

Gedefaw Getnet Amare

Keyword(s):

Antibacterial Activity ◽

Bacterial Infections ◽

Inhibition Zone ◽

Antibacterial Activities ◽

Maximum Activity ◽

New Drugs ◽

Diffusion Method ◽

Bacterial Strains ◽

Gram Positive ◽

Gram Negative

Objective. To evaluate the antibacterial effects of the leaf latex of Aloe weloensis against infectious bacterial strains. Methods. The leaf latex of A. weloensis at different concentrations (400, 500, and 600 mg/ml) was evaluated for antibacterial activities using the disc diffusion method against some Gram-negative species such as Escherichia coli (ATCC 14700) and Pseudomonas aeruginosa (ATCC 35619) and Gram-positive such as Staphylococcus aureus (ATCC 50080) and Enterococcus fecalis (ATCC 4623). Results. The tested concentrations of the latex ranging between 400 and 600 mg·mL−1 showed significant antibacterial activity against bacterial strain. The highest dose (600 mg/ml) of A. weloensis leaf latex revealed the maximum activity (25.93 ± 0.066 inhibition zone) followed by the dose 500 mg/ml against S. aureus. The lowest antibacterial activity was observed by the concentration 400 mg/ml (5.03 ± 0.03) against E. coli. Conclusion. The results of the present investigation suggest that the leaf latex of A. weloensis can be used as potential leads to discover new drugs to control some bacterial infections.

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Molecular Dynamics Simulation of the Interaction of Two Linear Battacin Analogs with Model Gram-Positive and Gram-Negative Bacterial Cell Membranes

ACS Omega ◽

10.1021/acsomega.0c04752 ◽

2020 ◽

Author(s):

Aparajita Chakraborty ◽

Elisey Kobzev ◽

Jonathan Chan ◽

Gayan Heruka de Zoysa ◽

Vijayalekshmi Sarojini ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Bacterial Cell ◽

Cell Membranes ◽

Dynamics Simulation ◽

Gram Positive ◽

Gram Negative

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Bacteriological profile and antibiogram of cancer patients admitted in intensive care unit of a tertiary care cancer hospital in central Kerala

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20205323 ◽

2020 ◽

Vol 8 (12) ◽

pp. 4450

Author(s):

Sanjana Ramakrishnan ◽

Sourabh Radhakrishnan ◽

Sonu Lazar Cyriac

Keyword(s):

Cancer Patients ◽

Bacterial Infections ◽

Tertiary Care ◽

Gram Positive ◽

Cross Sectional ◽

Gram Negative ◽

Mortality And Morbidity ◽

E Coli ◽

Resistance To Penicillin ◽

Study Laboratory

Background: Opportunistic bacterial infections remain a serious morbidity among cancer patients. This study was aimed to determine the bacteriological and antibiotic profile of cancer patients admitted to the ICU of a tertiary care centre.Methods: Cross sectional study was done among cancer patients admitted in the Oncology neutropenic ICU during the period from August 2017 to July 2019. All patients admitted with a proven diagnosis of cancer for whom at least one bacterial culture was sent from any site were included in the study. Laboratory on culture reports were obtained from patient files and analysed.Results: A total of 278 samples from 256 patients (60±11.6 years) were analysed. Among the 111/278 positive cultures, 29 were blood samples and 1 was a pleural fluid sample. Gram negative organisms were 62.1% with Escherichia coli (25, 36.2%) as prevalent. Among the 37.8% gram positives, Staphylococcus aureus (18. 42.8%) was prevalent. Most of the E. coli strains showed highest resistance to ceftazidime (96%) and highest sensitivity to amikacin. The commonest gram-positive organism, Staphylococcus species were 100 % sensitive to vancomycin and linezolid and 100 % resistance to penicillin. Conclusions: E. coli (gram negative) showed highest resistance to ceftazidime and sensitivity to amikacin. S. aureus (gram positive) was sensitive to vancomycin and linezolid and resistance to penicillin. An antibiogram for cancer patients helps the clinician to initiate an appropriate empirical antibiotic therapy to reduce mortality and morbidity.

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Efficacy of some medicated soaps and hand washes available in market

International Journal of Science and Research Archive ◽

10.30574/ijsra.2021.3.1.0098 ◽

2021 ◽

Vol 3 (1) ◽

pp. 047-055

Author(s):

Pimpliskar Mukesh ◽

SoumyaGounder ◽

Rahul Jadhav

Keyword(s):

Broad Spectrum ◽

Life Forms ◽

Small Scale ◽

Gram Positive ◽

Consistent Finding ◽

Gram Negative ◽

Cross Transmission ◽

Spectrum Activity ◽

Significant Measure ◽

Broad Spectrum Activity

Background: Handwashing is underlined as the absolute most significant measure to forestall cross-transmission of small-scale life forms and consequently to forestall nosocomial contaminations. Be that as it may, under routine emergency clinic practice consistent with this measure is still unsatisfactorily low, under half in many investigations distributed in the previous 20 years. This consistent finding is stressing because ongoing investigations have demonstrated that this degree of consistency won't decrease the danger of transmission of multi- medicate safe microscopic organisms in the emergency clinics. Results: In the present investigation effect of marketed hand washed namely Lifebuoy, Dettol and Savlon were tested on bacteria E. coli, S.aureus, S.pyogen, Klebshiella and, fungi Candida albicans. All the handwash at concentrated level found to be effective but only Dettol hand wash could give inhibitory action at 25ug/ml against Klebshiella while others at50ug/ml. Conclusions: Soapex and Dettol soap had broad spectrum activity as it inhibited the growth of Gram positive (Streptococcus pyogen) and Gram-negative (Escherichia coli). Liquid handwash such as Lifebuoy,Dettol and Savlon showed broad spectrum activity on both Gram-positive and Gram negative test microorganisms.

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Serum biomarkers to differentiate Gram-negative, Gram-positive and fungal infection in febrile patients

Journal of Medical Microbiology ◽

10.1099/jmm.0.001360 ◽

2021 ◽

Vol 70 (7) ◽

Author(s):

Dongguang Niu ◽

Qian Huang ◽

Fan Yang ◽

Weiliang Tian ◽

Chen Li ◽

...

Keyword(s):

Bloodstream Infection ◽

Bacterial Infections ◽

Fungal Infections ◽

Serum Levels ◽

Serum Biomarker ◽

Diagnostic Efficiency ◽

Gram Positive ◽

Gram Negative ◽

Neutrophil Lymphocyte Ratio ◽

Bacteria And Fungi

Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required. Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G−) bacteria from Gram-positive (G+) bacteria and fungi in febrile patients. Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G− group (n=188), a G+ group (n=168), a fungal group (n=38) and a culture negative group (n=173). Sensitivity, specificity, Yuden’s index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens. Results. Serum IL-6 and PCT in the G− group increased significantly when compared with both the G+ group and fungal group (P <0.05). AUC of IL-6 (0.767, 95 % CI:0.725–0.805) is higher than AUC of PCT (0.751, 95 % CI:0.708–0.796) in discriminating the G− group from G+ group. When discriminating the G− group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651–0.747) with a cut-off value of 464.3 pg ml−1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585–0.688) with a cut-off value of 0.68 ng ml−1. Additionally, AUC of NLR (0.685, 95 % CI:0.646–0.727) in discriminating the fungal group from G+ group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP. Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.

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TSPphg Lysin from the Extremophilic Thermus Bacteriophage TSP4 as a Potential Antimicrobial Agent against Both Gram-Negative and Gram-Positive Pathogenic Bacteria

Viruses ◽

10.3390/v12020192 ◽

2020 ◽

Vol 12 (2) ◽

pp. 192 ◽

Cited By ~ 6

Author(s):

Feng Wang ◽

Xinyu Ji ◽

Qiupeng Li ◽

Guanling Zhang ◽

Jiani Peng ◽

...

Keyword(s):

Bacterial Infections ◽

Pathogenic Bacteria ◽

Infection Model ◽

Bacterial Cells ◽

Skin Damage ◽

Gram Positive ◽

Antibiotic Resistant ◽

Gram Negative

New strategies against antibiotic-resistant bacterial pathogens are urgently needed but are not within reach. Here, we present in vitro and in vivo antimicrobial activity of TSPphg, a novel phage lysin identified from extremophilic Thermus phage TSP4 by sequencing its whole genome. By breaking down the bacterial cells, TSPphg is able to cause bacteria destruction and has shown bactericidal activity against both Gram-negative and Gram-positive pathogenic bacteria, especially antibiotic-resistant strains of Klebsiella pneumoniae, in which the complete elimination and highest reduction in bacterial counts by greater than 6 logs were observed upon 50 μg/mL TSPphg treatment at 37 °C for 1 h. A murine skin infection model further confirmed the in vivo efficacy of TSPphg in removing a highly dangerous and multidrug-resistant Staphylococcus aureus from skin damage and in accelerating wound closure. Together, our findings may offer a therapeutic alternative to help fight bacterial infections in the current age of mounting antibiotic resistance, and to shed light on bacteriophage-based strategies to develop novel anti-infectives.

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Induction of murine peritoneal gamma/delta T cells and their role in resistance to bacterial infection.

Journal of Experimental Medicine ◽

10.1084/jem.178.3.971 ◽

1993 ◽

Vol 178 (3) ◽

pp. 971-984 ◽

Cited By ~ 83

Author(s):

M J Skeen ◽

H K Ziegler

Keyword(s):

T Cells ◽

T Cell ◽

Peritoneal Cavity ◽

Gamma Delta T Cells ◽

Gamma Delta ◽

Gram Positive ◽

Gram Negative ◽

A Site ◽

Gamma Delta T Cell

Previous studies have reported an association of gamma/delta T cells with microbial infection in both human lesions and murine infectious disease models. In this study we provide a comprehensive analysis of the conditions under which the induction of gamma/delta T cells occurs at a site of infection. We found a site-specific induction of gamma/delta T cells after the injection of Listeria monocytogenes in the peritoneal cavity of C3H mice. No changes were seen in the splenic or lymph node populations after these injections. Both the proportion and the absolute number of gamma/delta T cells increased in the peritoneal cavity. Additionally, when peritoneal T cells from Listeria-immune mice were restimulated in vitro, the induced gamma/delta T cells exhibited a greater expansion potential than the alpha/beta T cells. Neither the induced gamma/delta T cells nor those from normal mice expressed CD4 or CD8 on the cell surface. Thy-1 was expressed on only 29% of normal peritoneal gamma/delta T cells, but after intraperitoneal Listeria injection 65% of induced gamma/delta T cells expressed. Thy-1, Pgp-1 and CD45R expression on both normal and induced gamma/delta T cells was consistent with an activation phenotype. Significant increases in peritoneal gamma/delta T cells were not seen until 5-7 d after Listeria injection. The proportion of the CD3+ population expressing the gamma/delta T cell receptor remained elevated for 6-7 wk, while the absolute numbers of peritoneal gamma/delta T cells declined gradually over this time period, reflecting a decrease in both the number of lymphocytes and the percentage of these that were CD3+. Peak numbers of gamma/delta T cells were seen at day 10 with live microbes such as Listeria. A variety of microbes, toxins, mitogens, antigens, cytokines, and nonspecific inflammatory agents were evaluated for their ability to induce gamma/delta T cells in the peritoneal cavity. Both Gram-positive and Gram-negative bacteria as well as Mycobacteria were able to induce gamma/delta T cells that showed increased in vitro expansion potential. An exotoxin from a Gram-positive organism, listeriolysin-o, and the lipopolysaccharide (LPS) endotoxin from a Gram-negative organism were also effective. gamma/delta T cell responses to LPS were under lps gene control. Peak numbers of gamma/delta T cells were observed at day 3 after injection with exotoxins and endotoxins. Modifications that abrogated the virulence of a bacterial strain also eliminated the inductive effect for gamma/delta T cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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Non-toxic Cobalt(III) Schiff Base Complexes with Broad Spectrum Antifungal Activity

10.26434/chemrxiv.12736505 ◽

2020 ◽

Author(s):

Angelo Frei ◽

A. Paden King ◽

Gabrielle J. Lowe ◽

Amy K. Cain ◽

Francesca L. Short ◽

...

Keyword(s):

Schiff Base ◽

Antifungal Activity ◽

Broad Spectrum ◽

Bacterial Infections ◽

Fungal Infections ◽

Antifungal Drugs ◽

New Drugs ◽

Schiff Base Complexes ◽

In Vivo Studies

Resistance to currently available antifungal drugs has quietly been on the rise but overshadowed by the alarming spread of antibacterial resistance. There is a striking lack of attention to the threat of drug resistant fungal infections, with only a handful of new drugs currently in development. Given that metal complexes have proven to be useful new chemotypes in the fight against diseases such as cancer, malaria, and bacterial infections, it stands to reason to explore their possible utility in treating fungal infections. Herein we report a series of cobalt(III) Schiff base complexes with broad spectrum antifungal activity. Some of these complexes (1-3) show minimum inhibitory concentrations (MIC) in the low micro- to nanomolar range against a series of Candida and Cryptococcus yeasts. Additionally, we demonstrate that these compounds show no cytotoxicity against both bacterial and human cells. Finally, we report first in vivo toxicity data on these compounds in Galleria mellonella, showing that doses as high as 266 mg/kg are tolerated without adverse effects, paving the way for further in vivo studies of these complexes. <br>

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Potential Assessment of Rumex spp. as a Source of Bioactive Compounds and Biological Activity

Biointerface Research in Applied Chemistry ◽

10.33263/briac122.18241834 ◽

2021 ◽

Vol 12 (2) ◽

pp. 1824-1834

Keyword(s):

Antioxidant Activity ◽

Broad Spectrum ◽

Pathogenic Bacteria ◽

Gram Negative Bacteria ◽

Meoh Extract ◽

Gram Positive ◽

Filter Paper Disc ◽

Gram Negative ◽

Gram Positive Bacteria ◽

Antibacterial Performance

Secondary metabolites from the shoots and roots of three Rumex species collected from three different habitats were investigated (Rumex dentatus collected from cultivated land, R. pictus collected from the coastal desert and R. vesicarius collected from the inland desert) and tested for antioxidant activity as well as for anti-microbial activity against some human pathogenic bacteria. The present study indicated that the quantitative analysis of shoot and root extracts of three Rumex spp. were found to be rich in tannins and phenolics composition. The aerial parts of the three plants exhibited the highest significant values compared to the root parts. The MeOH extracts of Rumex species showed adequate antioxidant activity, wherein the IC50 values of the MeOH from the cultivated sample was 41.61 and 31.31 mg mL-1, coastal samples were 34.99 and 23.99 mg mL-1, while the sample of inland showed IC50 value of 41.59 and 31.67 mg mL-1, for root and shoot, respectively. Furthermore, using a filter paper disc assay, the MeOH extracts of the three Rumex species showed a substantial anti-microbial inhibitory effect on the growth of 10 pathogenic bacteria. According to sensitivity, the tested organisms could be sequenced as following: E. coli < K. pneumoniae ˂ S. typhi < P. aeruginosa for Gram-negative bacteria and B. subtilis < S. pneumoniae ˂ L. monocytoyenes < S. epidermis < S. aureus < B. cereus for Gram-positive bacteria. In addition, the antibacterial performance of R. dentatus root and R. vesicarius shoot MeOH extract is 100% broad spectrum against Gram-negative bacteria. A shoot of R. dentatus and R. pictus MeOH extract against Gram-positive bacteria is 83.3% broad spectrum. A further study is recommended for more characterization of the major compounds and assesses their efficiency and biosafety.

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