Bacteria Are New Targets for Inhibitors of Human Farnesyltransferase

Farnesyltransferase inhibitors (FTIs) are focus for the treatment of several diseases, particularly in the field of cancer therapy. Their potential, however, goes even further, as a number of studies have evaluated FTIs for the treatment of infectious diseases such as malaria, African sleeping sickness, leishmaniosis, and hepatitis D virus infection. Little is known about protein prenylation mechanisms in human pathogens. However, disruption of IspA, a gene encoding the geranyltranstransferase of Staphylococcus aureus (S. aureus) leads to reprogramming of cellular behavior as well as impaired growth and decreased resistance to cell wall-targeting antibiotics. We used an agar well diffusion assay and a time kill assay and determined the minimum inhibitory concentrations of the FTIs lonafarnib and tipifarnib. Additionally, we conducted cell viability assays. We aimed to characterize the effect of these FTIs on S. aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (S. epidermidis), Escherichia coli (E. coli), Enterococcus faecium (E. faecium), Klebsiella pneumoniae (K. pneumoniae), Pseudomonas aeruginosa (P. aeruginosa), and Streptococcus pneumoniae (S. pneumoniae). Both the FTIs lonafarnib and tipifarnib were capable of inhibiting the growth of the Gram-positive bacteria S. aureus, MRSA, S. epidermidis, and S. pneumoniae, whereas no effect was observed on Gram-negative bacteria. The analysis of the impact of lonafarnib and tipifarnib on common human pathogens might lead to novel insights into their defense mechanisms and therefore provide new therapeutic targets for antibiotic-resistant bacterial infections.

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Staphylococcus aureus Arsenal To Conquer the Lower Respiratory Tract

mSphere ◽

10.1128/msphere.00059-21 ◽

2021 ◽

Vol 6 (3) ◽

Author(s):

Mariane Pivard ◽

Karen Moreau ◽

François Vandenesch

Keyword(s):

Staphylococcus Aureus ◽

Respiratory Tract ◽

Virulence Factors ◽

Lower Respiratory Tract ◽

Defense Mechanisms ◽

Future Research ◽

Epithelial Barrier ◽

Content Type ◽

Wide Range ◽

The Impact

ABSTRACT Staphylococcus aureus is both a commensal and a pathogenic bacterium for humans. Its ability to induce severe infections is based on a wide range of virulence factors. S. aureus community-acquired pneumonia (SA-CAP) is rare and severe, and the contribution of certain virulence factors in this disease has been recognized over the past 2 decades. First, the factors involved in metabolism adaptation are crucial for S. aureus survival in the lower respiratory tract, and toxins and enzymes are required for it to cross the pulmonary epithelial barrier. S. aureus subsequently faces host defense mechanisms, including the epithelial barrier, but most importantly the immune system. Here, again, S. aureus uses myriad virulence factors to successfully escape from the host’s defenses and takes advantage of them. The impact of S. aureus virulence, combined with the collateral damage caused by an overwhelming immune response, leads to severe tissue damage and adverse clinical outcomes. In this review, we summarize step by step all of the S. aureus factors implicated in CAP and described to date, and we provide an outlook for future research.

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Staphylococcus aureus Bacteremia in Patients Infected With COVID-19: A Case Series

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa518 ◽

2020 ◽

Vol 7 (11) ◽

Author(s):

Jaclyn A Cusumano ◽

Amy C Dupper ◽

Yesha Malik ◽

Elizabeth M Gavioli ◽

Jaspreet Banga ◽

...

Keyword(s):

New York ◽

Staphylococcus Aureus ◽

New York City ◽

Hospital Mortality ◽

Bacterial Infections ◽

Case Series ◽

Mortality Rates ◽

Day Hospital ◽

Staphylococcus Aureus Bacteremia ◽

The Impact

Abstract Background Previous viral pandemics have shown that secondary bacterial infections result in higher morbidity and mortality, with Staphylococcus aureus being the primary causative pathogen. The impact of secondary S. aureus bacteremia on mortality in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unknown. Methods This was a retrospective observational case series of patients with coronavirus disease 2019 (COVID-19) who developed secondary S. aureus bacteremia across 2 New York City hospitals. The primary end point was to describe 14-day and 30-day hospital mortality rates of patients with COVID-19 and S. aureus bacteremia. Secondary end points included predictors of 14-day and 30-day hospital mortality in patients with COVID-19 and S. aureus bacteremia. Results A total of 42 patients hospitalized for COVID-19 with secondary S. aureus bacteremia were identified. Of these patients, 23 (54.8%) and 28 (66.7%) died at 14 days and 30 days, respectively, from their first positive blood culture. Multivariate analysis identified hospital-onset bacteremia (≥4 days from date of admission) and age as significant predictors of 14-day hospital mortality and Pitt bacteremia score as a significant predictor of 30-day hospital mortality (odds ratio [OR], 11.9; 95% CI, 2.03–114.7; P = .01; OR, 1.10; 95% CI, 1.03–1.20; P = .02; and OR, 1.56; 95% CI, 1.19–2.18; P = .003, respectively). Conclusions Bacteremia with S. aureus is associated with high mortality rates in patients hospitalized with COVID-19. Further investigation is warranted to understand the impact of COVID-19 and secondary S. aureus bacteremia.

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Production of Interleukin-12 by Murine Macrophages in Response to Bacterial Peptidoglycan

Infection and Immunity ◽

10.1128/iai.66.10.4947-4949.1998 ◽

1998 ◽

Vol 66 (10) ◽

pp. 4947-4949 ◽

Cited By ~ 29

Author(s):

Christine Lawrence ◽

Charles Nauciel

Keyword(s):

Staphylococcus Aureus ◽

Host Defense ◽

Defense Mechanisms ◽

Bacterial Infections ◽

Micrococcus Luteus ◽

Delayed Type Hypersensitivity ◽

Interleukin 12 ◽

Hypersensitivity Reactions ◽

Mouse Macrophages ◽

Bacterial Peptidoglycan

ABSTRACT Peptidoglycan (PG), a component of the bacterial cell wall, has various immunomodulating activities, including the capacity to induce delayed-type hypersensitivity reactions to antigens administered in Freund’s adjuvant. We report that PG induces interleukin-12 (IL-12) mRNA production and IL-12 secretion by mouse macrophages. The capacity of PG to induce IL-12 production, like its previously reported immunomodulating activities, was dependent on the structure of its peptide subunit. PG from Bacillus megaterium andStaphylococcus aureus induced IL-12 production, whereas PG from Micrococcus luteus and Corynebacterium poinsettiae did not. The ability of most bacterial PGs to induce IL-12 production suggests that they play an important role in triggering host defense mechanisms against bacterial infections.

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Clinical outcomes in patients co-infected with COVID-19 and Staphylococcus aureus: a scoping review

BMC Infectious Diseases ◽

10.1186/s12879-021-06616-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jenna R. Adalbert ◽

Karan Varshney ◽

Rachel Tobin ◽

Rafael Pajaro

Keyword(s):

Staphylococcus Aureus ◽

Hospital Admission ◽

Clinical Outcomes ◽

Scoping Review ◽

Bacterial Infections ◽

Final Analysis ◽

Mortality Rates ◽

Hospital Environment ◽

Review Of The Literature ◽

The Impact

Abstract Background Endemic to the hospital environment, Staphylococcus aureus (S. aureus) is a leading bacterial pathogen that causes deadly infections such as bacteremia and endocarditis. In past viral pandemics, it has been the principal cause of secondary bacterial infections, significantly increasing patient mortality rates. Our world now combats the rapid spread of COVID-19, leading to a pandemic with a death toll greatly surpassing those of many past pandemics. However, the impact of co-infection with S. aureus remains unclear. Therefore, we aimed to perform a high-quality scoping review of the literature to synthesize the existing evidence on the clinical outcomes of COVID-19 and S. aureus co-infection. Methods A scoping review of the literature was conducted in PubMed, Scopus, Ovid MEDLINE, CINAHL, ScienceDirect, medRxiv, and the WHO COVID-19 database using a combination of terms. Articles that were in English, included patients infected with both COVID-19 and S. aureus, and provided a description of clinical outcomes for patients were eligible. From these articles, the following data were extracted: type of staphylococcal species, onset of co-infection, patient sex, age, symptoms, hospital interventions, and clinical outcomes. Quality assessments of final studies were also conducted using the Joanna Briggs Institute’s critical appraisal tools. Results Searches generated a total of 1922 publications, and 28 articles were eligible for the final analysis. Of the 115 co-infected patients, there were a total of 71 deaths (61.7%) and 41 discharges (35.7%), with 62 patients (53.9%) requiring ICU admission. Patients were infected with methicillin-sensitive and methicillin-resistant strains of S. aureus, with the majority (76.5%) acquiring co-infection with S. aureus following hospital admission for COVID-19. Aside from antibiotics, the most commonly reported hospital interventions were intubation with mechanical ventilation (74.8 %), central venous catheter (19.1 %), and corticosteroids (13.0 %). Conclusions Given the mortality rates reported thus far for patients co-infected with S. aureus and COVID-19, COVID-19 vaccination and outpatient treatment may be key initiatives for reducing hospital admission and S. aureus co-infection risk. Physician vigilance is recommended during COVID-19 interventions that may increase the risk of bacterial co-infection with pathogens, such as S. aureus, as the medical community’s understanding of these infection processes continues to evolve.

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Global Transcriptome Analysis of Staphylococcus aureus Biofilms in Response to Innate Immune Cells

Infection and Immunity ◽

10.1128/iai.00819-13 ◽

2013 ◽

Vol 81 (12) ◽

pp. 4363-4376 ◽

Cited By ~ 34

Author(s):

Tyler D. Scherr ◽

Christelle M. Roux ◽

Mark L. Hanke ◽

Amanda Angle ◽

Paul M. Dunman ◽

...

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

Defense Mechanisms ◽

Bacterial Infections ◽

Expression Patterns ◽

Immune Defense ◽

Innate Immune ◽

Gene Expression Patterns ◽

Content Type ◽

Affymetrix Microarrays

ABSTRACTThe potent phagocytic and microbicidal activities of neutrophils and macrophages are among the first lines of defense against bacterial infections. YetStaphylococcus aureusis often resistant to innate immune defense mechanisms, especially when organized as a biofilm. To investigate howS. aureusbiofilms respond to macrophages and neutrophils, gene expression patterns were profiled using Affymetrix microarrays. The addition of macrophages toS. aureusstatic biofilms led to a global suppression of the biofilm transcriptome with a wide variety of genes downregulated. Notably, genes involved in metabolism, cell wall synthesis/structure, and transcription/translation/replication were among the most highly downregulated, which was most dramatic at 1 h compared to 24 h following macrophage addition to biofilms. Unexpectedly, few genes were enhanced in biofilms after macrophage challenge. Unlike coculture with macrophages, coculture ofS. aureusstatic biofilms with neutrophils did not greatly influence the biofilm transcriptome. Collectively, these experiments demonstrate thatS. aureusbiofilms differentially modify their gene expression patterns depending on the leukocyte subset encountered.

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Insight on the Structure-to-Activity of Carbosilane Metallodendrimers in the Fight against Staphylococcus aureus Biofilms

Antibiotics ◽

10.3390/antibiotics10050589 ◽

2021 ◽

Vol 10 (5) ◽

pp. 589

Author(s):

Celia Llamazares ◽

Natalia Sanz del Olmo ◽

Juan Soliveri ◽

F. Javier de la Mata ◽

José Luis Copa-Patiño ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Biofilm Formation ◽

Metal Ion ◽

Bacterial Infections ◽

Structural Parameters ◽

Health Concern ◽

Relevant Parameter ◽

Meta Position ◽

Imine Bond ◽

The Impact

Biofilm formation is a critical health concern, involved in most human bacterial infections. Combatting this mechanism, which increases resistance to traditional antibiotics and host immune defences, requires novel therapeutic approaches. The remarkable biocide activity and the monodispersity of carbosilane metallodendrimers make them excellent platforms to evaluate the impact of different structural parameters on the biological activity. In this work, we explore the influence of iminopyridine ring substituents on the antibacterial activity against planktonic and biofilm Staphylococcus aureus. New families of first-generation Ru(II) and Cu(II) metallodendrimers were synthesised and analysed, in comparison to the non-substituted counterparts. The results showed that the presence of methyl or methoxy groups in meta position to the imine bond decreased the overall positive charge on the metal ion and, subsequently, the activity against planktonic bacteria. However, it seemed a relevant parameter to consider for the prevention of biofilm formation, if they contribute to increasing the overall lipophilicity. An optimum balance of the charge and lipophilicity of the metallodrug, accomplished through structural design, will provide effective biocide agents against bacteria biofilms.

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Characterization and Selection of Lactobacillus plantarum and Lactobacillus paracasei for prevention of oral bacterial infections from Chinese pickle

AMB Express ◽

10.1186/s13568-021-01245-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Guochao Jia ◽

Xiaofeng Liu ◽

Aimin Zhi ◽

Jingjing Li ◽

Yuanfeng Wu ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Lactobacillus Plantarum ◽

Bacterial Infections ◽

Pathogenic Bacteria ◽

Skim Milk ◽

Lactobacillus Paracasei ◽

Probiotic Properties ◽

Oral Infections ◽

Bacterial Surface ◽

Agar Well Diffusion Assay

AbstractThe oral infections were mainly caused by Streptococci and Staphylococcus aureus. Antibiotic therapies can eliminate these harmful bacteria. However, it can break beneficial microbes and lead to the persistence of resistant strains. The objective of our study was to select potential probiotic strains for the prevention of oral bacterial infections and evaluate their potential probiotic properties in oral cavity. AR113 (Lactobacillus plantarum) and AR340 (Lactobacillus paracasei) with significantly antimicrobial β-hemolytic streptococci and Staphylococcus aureus activity were isolated from Chinese pickle through agar well diffusion assay. Through the analyses of probiotic properties in antibiofilm, lysozyme and hydrogen peroxide tolerance, bacterial surface properties, adherence ability, tooth degradation and anti-inflammatory activity, the AR113 and AR340 showed anti-adhesion activity of 45.2–71.1% and 20.3–56.8% against β-hemolytic streptococci and 15.4–52.6% and 30.7–65.9% against Staphylococcus aureus, respectively, at different concentration. The two strains with high hydrophobicity, autoaggregation and survival rate adhered strongly to FaDu cells. AR113 and AR340 exhibited low calcium released from teeth (0.04 μg/mL and 0.03 μg/mL, respectively). ELISA analysis showed that AR113 and AR340 significantly inhibited the LPS-induced increase of NO and TNF-α expression. Strains-fermented skim milk inhibited the growth of β-hemolytic streptococci or Staphylococcus aureus. AR113 and AR340 were considered as probiotic candidates because of their higher antibacterial activity against some oral pathogenic bacteria, no potential of primitive cariogenicity. These candidates were expected as new probiotics with potential oral health benefits and no harmful effects.

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Phylogeny Characterization of Seb Gene Encoding Enterotoxins in Staphylococcus aureus Isolated from Raw Milk and Cheese

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.v9i3.13 ◽

2019 ◽

Vol 9 (o3) ◽

Author(s):

Fatima N. Aziz ◽

Laith Abdul Hassan Mohammed-Jawad

Keyword(s):

Staphylococcus Aureus ◽

Food Poisoning ◽

Raw Milk ◽

Staphylococcal Enterotoxin B ◽

Human Pathogen ◽

Conventional Pcr ◽

Biochemical Tests ◽

Specific Primers ◽

Gene Encoding

Food poisoning due to the bacteria is a big global problem in economically and human's health. This problem refers to an illness which is due to infection or the toxin exists in nature and the food that use. Milk is considered a nutritious food because it contains proteins and vitamins. The aim of this study is to detect and phylogeny characterization of staphylococcal enterotoxin B gene (Seb). A total of 200 milk and cheese samples were screened. One hundred ten isolates of Staphylococcus aureus pre-confirmed using selective and differential media with biochemical tests. Genomic DNA was extracted from the isolates and the SEB gene detects using conventional PCR with specific primers. Three staphylococcus aureus isolates were found to be positive for Seb gene using PCR and confirmed by sequencing. Sequence homology showed variety range of identity starting from (100% to 38%). Phylogenetic tree analyses show that samples (6 and 5) are correlated with S. epidermidis. This study discovered that isolates (A6-RLQ and A5-RLQ) are significantly clustered in a group with non- human pathogen Staphylococcus agnetis.

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Garlic Extract (Allium sativum L.) Effectively Inhibits Staphylococcus aureus and Escherichia coli by Invitro Test

Tropical Health and Medical Research ◽

10.35916/thmr.v0i0.22 ◽

2020 ◽

Vol 2 (2) ◽

pp. 61-68

Author(s):

Agnina Listya Anggraini ◽

Ratih Dewi Dwiyanti ◽

Anny Thuraidah

Keyword(s):

Escherichia Coli ◽

Staphylococcus Aureus ◽

Bacterial Infections ◽

Allium Sativum ◽

Antibacterial Properties ◽

Herbal Medicines ◽

Garlic Extract ◽

Dilution Method ◽

Initial Stage

Infection is a disease caused by the presence of pathogenic microbes, including Staphylococcus aureus and Escherichia coli. Garlic (Allium sativum L.) has chemical contents such as allicin, alkaloids, flavonoids, saponins, tannins, and steroids, which can function as an antibacterial against Staphylococcus aureus and Escherichia coli. This study aims to determine the antibacterial properties of garlic extract powder against Staphylococcus aureus and Escherichia coli. This research is the initial stage of the development of herbal medicines to treat Staphylococcus aureus and Escherichia coli infections. The antibacterial activity test was carried out by the liquid dilution method. The concentrations used were 30 mg/mL, 40 mg/mL, 50 mg/mL, 60 mg/mL and 70 mg/mL. The results showed that the Minimum Inhibitory Concentration (MIC) against Staphylococcus aureus and Escherichia coli was 40 mg/mL and 50 mg / mL. Minimum Bactericidal Concentration (MBC) results for Staphylococcus aureus and Escherichia coli are 50 mg/mL and 70 mg/mL. Based on the Simple Linear Regression test, the R2 value of Staphylococcus aureus and Escherichia coli is 0.545 and 0.785, so it can be concluded that there is an effect of garlic extract powder on the growth of Staphylococcus aureus and Escherichia coli by 54.5% and 78.5%. Garlic (Allium sativum L.) extract powder has potential as herbal medicine against bacterial infections but requires further research to determine its effect in vivo.

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The Impact of Plant Bioactive Compounds on Aging and Fertility of Diverse Organisms: A Review

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200429101942 ◽

2020 ◽

Vol 20 (13) ◽

pp. 1287-1299

Author(s):

Muhammad Akram Mohd Noordin ◽

Mahanem Mat Noor ◽

Wan Mohd Aizat

Keyword(s):

Clinical Trial ◽

Bioactive Compounds ◽

Defense Mechanisms ◽

Healthy Aging ◽

Antioxidant Defense ◽

Senior Citizens ◽

Aging Population ◽

Human Clinical Trial ◽

Fertility Reduction ◽

The Impact

It is expected that in 2050, there will be more than 20% of senior citizens aged over 60 years worldwide. Such alarming statistics require immediate attention to improve the health of the aging population. Since aging is closely related to the loss of antioxidant defense mechanisms, this situation eventually leads to numerous health problems, including fertility reduction. Furthermore, plant extracts have been used in traditional medicine as potent antioxidant sources. Although many experiments had reported the impact of various bioactive compounds on aging or fertility, there is a lack of review papers that combine both subjects. In this review, we have collected and discussed various bioactive compounds from 26 different plant species known to affect both longevity and fertility. These compounds, including phenolics and terpenes, are mostly involved in the antioxidant defense mechanisms of diverse organisms such as rats, mites, fruit flies, roundworms, and even roosters. A human clinical trial should be considered in the future to measure the effects of these bioactive compounds on human health and longevity. Ultimately, these plant-derived compounds could be developed into health supplements or potential medical drugs to ensure a healthy aging population.

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