scholarly journals Koala cathelicidin PhciCath5 has antimicrobial activity, including against Chlamydia pecorum

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249658
Author(s):  
Emma Peel ◽  
Yuanyuan Cheng ◽  
Julianne T. Djordjevic ◽  
Denis O’Meally ◽  
Mark Thomas ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Electrostatic Interactions ◽  
Reproductive Tract ◽  
Significant Loss ◽  
The Body ◽  
Chlamydia Pecorum ◽  
Peptide Family ◽  
Tract Disease ◽  
Bacteria And Fungi

Devastating fires in Australia over 2019–20 decimated native fauna and flora, including koalas. The resulting population bottleneck, combined with significant loss of habitat, increases the vulnerability of remaining koala populations to threats which include disease. Chlamydia is one disease which causes significant morbidity and mortality in koalas. The predominant pathogenic species, Chlamydia pecorum, causes severe ocular, urogenital and reproductive tract disease. In marsupials, including the koala, gene expansions of an antimicrobial peptide family known as cathelicidins have enabled protection of immunologically naïve pouch young during early development. We propose that koala cathelicidins are active against Chlamydia and other bacteria and fungi. Here we describe ten koala cathelicidins, five of which contained full length coding sequences that were widely expressed in tissues throughout the body. Focusing on these five, we investigate their antimicrobial activity against two koala C. pecorum isolates from distinct serovars; MarsBar and IPTaLE, as well as other bacteria and fungi. One cathelicidin, PhciCath5, inactivated C. pecorum IPTaLE and MarsBar elementary bodies and significantly reduced the number of inclusions compared to the control (p<0.0001). Despite evidence of cathelicidin expression within tissues known to be infected by Chlamydia, natural PhciCath5 concentrations may be inadequate in vivo to prevent or control C. pecorum infections in koalas. PhciCath5 also displayed antimicrobial activity against fungi and Gram negative and positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Electrostatic interactions likely drive PhciCath5 adherence to the pathogen cell membrane, followed by membrane permeabilisation leading to cell death. Activity against E. coli was reduced in the presence of 10% serum and 20% whole blood. Future modification of the PhciCath5 peptide to enhance activity, including in the presence of serum/blood, may provide a novel solution to Chlamydia infection in koalas and other species.

scholarly journals Bacteriostatic and Bactericidal Effect of Tigecycline on Leptospira spp.

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 467
Author(s):  
Fabrizio Bertelloni ◽  
Giovanni Cilia ◽  
Filippo Fratini
Keyword(s):  
Antimicrobial Activity ◽  
Urinary Tract ◽  
Inhibitory Concentration ◽  
Minimum Bactericidal Concentration ◽  
Bactericidal Effect ◽  
Leptospira Spp ◽  
Tract Disease ◽  
Few Data ◽  
Reference Strains

Tigecycline is a relatively new antimicrobial, belonging to glycylcyclines with antimicrobial activity against a large spectrum of bacteria. Very few data are available on its effect on Leptospira spp., which consist in a bacteriostatic mechanism. The aim of this investigation was to evaluate the bacteriostatic and bactericidal effect of tigecycline on reference Leptospira strains belonging to 16 serovars. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined through the microdilutions method, and tetracycline was used as the control. Results showed that tigecycline had higher MIC and MBC values than tetracycline. Obtained MIC values were between 4 and 32 µg/mL, while MBC values between 16 and >128 µg/mL. Patoc (MIC: 4 µg/mL; MBC: 16 µg/mL) resulted in the most susceptible serovar, while the most resistant were Bataviae (MIC: 32 µg/mL; MBC: 64 µg/mL), Bratislava (MIC: 8 µg/mL; MBC 128 µg/mL), and Tarassovi (MIC: 8 µg/mL; MBC: >128 µg/mL). This is the first investigation focused on the effect of tigecycline against Leptospira spp. reference strains. Since tigecycline is used as a treatment for bacteremia and urinary tract disease, and these symptoms could be linked to Leptospira infection, the possibility of using this antibiotic as a treatment for leptospirosis should be evaluated. Further studies are needed to explore the possibility to use tigecycline for in vivo application against Leptospira.

scholarly journals A Systematic Study of the Stability, Safety, and Efficacy of the de novo Designed Antimicrobial Peptide PepD2 and Its Modified Derivatives Against Acinetobacter baumannii

2021 ◽  
Vol 12 ◽  
Author(s):  
Sung-Pang Chen ◽  
Eric H-L Chen ◽  
Sheng-Yung Yang ◽  
Pin-Shin Kuo ◽  
Hau-Ming Jan ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptide ◽  
Acinetobacter Baumannii ◽  
De Novo ◽  
Multidrug Resistant ◽  
Hek293 Cells ◽  
Amino Acid Residues ◽  
Bacteria And Fungi ◽  
The Stability

Searching for new antimicrobials is a pressing issue to conquer the emergence of multidrug-resistant (MDR) bacteria and fungi. Antimicrobial peptides (AMPs) usually have antimicrobial mechanisms different from those of traditional antibiotics and bring new hope in the discovery of new antimicrobials. In addition to antimicrobial activity, stability and target selectivity are important concerns to decide whether an antimicrobial peptide can be applied in vivo. Here, we used a simple de novo designed peptide, pepD2, which contains only three kinds of amino acid residues (W, K, L), as an example to evaluate how the residues and modifications affect the antimicrobial activity against Acinetobacter baumannii, stability in plasma, and toxicity to human HEK293 cells. We found that pepI2 with a Leu→Ile substitution can decrease the minimum bactericidal concentrations (MBC) against A. baumannii by one half (4 μg/mL). A D-form peptide, pepdD2, in which the D-enantiomers replaced the L-enantiomers of the Lys(K) and Leu(L) residues, extended the peptide half-life in plasma by more than 12-fold. PepD3 is 3-residue shorter than pepD2. Decreasing peptide length did not affect antimicrobial activity but increased the IC50 to HEK293 cells, thus increased the selectivity index (SI) between A. baumannii and HEK293 cells from 4.7 to 8.5. The chain length increase of the N-terminal acyl group and the Lys→Arg substitution greatly enhanced the hemolytic activity, hence those modifications are not good for clinical application. Unlike colistin, the action mechanism of our peptides relies on negatively charged lipids rather than lipopolysaccharides. Therefore, not only gram-negative bacteria but also gram-positive bacteria can be killed by our peptides.

Overbrowsing, and decline of a population of the koala, Phascolarctos cinereus, in Victoria. II. Population condition

1985 ◽  
Vol 12 (3) ◽  
pp. 367 ◽  
Author(s):  
R. W. Martin
Keyword(s):  
Growth Rates ◽  
Reproductive Tract ◽  
The Body ◽  
Low Fertility ◽  
Age Classes ◽  
Lower Growth ◽  
Phascolarctos Cinereus ◽  
Significant Difference ◽  
Body Weights ◽  
Tract Disease

Juvenile and sub-adult koalas from a population at Walkerville, Victoria, which was severely defoliating its preferred food trees, had significantly lower growth rates than animals from a population on French Island, Victoria. Mature males from Walkerville were significantly smaller than French Island males in most age classes. There was no significant difference between the body weights of mature females of the 2 populations. Haematological tests on the females showed that nutritionally induced anaemia was significant in the Walkerville animals by Jan. 1981. Heavy tick loads probably exacerbated the effects of the food shortage on the animals' condition, but were not the cause of the anaemia. The low fertility rate of the Walkerville females appeared to be due to their poor nutritional state and to reproductive tract disease.

scholarly journals Transcriptional response of Mycoplasma genitalium to osmotic stress

Microbiology ◽  
2011 ◽  
Vol 157 (2) ◽  
pp. 548-556 ◽  
Author(s):  
Wenbo Zhang ◽  
Joel B. Baseman
Keyword(s):  
Reproductive Tract ◽  
Osmotic Shock ◽  
Transcriptional Response ◽  
Mycoplasma Genitalium ◽  
Protein Translation ◽  
Environmental Signals ◽  
Associated Proteins ◽  
Transcriptional Changes ◽  
Tract Disease

Mycoplasma genitalium is the causative agent of non-gonococcal, chlamydia-negative urethritis in men and has been linked to reproductive tract disease syndromes in women. As with other mycoplasmas, M. genitalium lacks many regulatory genes because of its streamlined genome and total dependence on a parasitic existence. Therefore, it is important to understand how gene regulation occurs in M. genitalium, particularly in response to environmental signals likely to be encountered in vivo. In this study, we developed an oligonucleotide-based microarray to investigate transcriptional changes in M. genitalium following osmotic shock. Using a physiologically relevant osmolarity condition (0.3 M sodium chloride), we identified 39 upregulated and 72 downregulated genes. Of the upregulated genes, 21 were of unknown function and 15 encoded membrane-associated proteins. The majority of downregulated genes encoded enzymes involved in energy metabolism and components of the protein translation process. These data provide insights into the in vivo response of M. genitalium to hyperosmolarity conditions and identify candidate genes that may contribute to mycoplasma survival in the urogenital tract.

scholarly journals Intrastrain Heterogeneity of the mgpB Gene in Mycoplasma genitalium Is Extensive In Vitro and In Vivo and Suggests that Variation Is Generated via Recombination with Repetitive Chromosomal Sequences

2006 ◽  
Vol 74 (7) ◽  
pp. 3715-3726 ◽  
Author(s):  
Stefanie L. Iverson-Cabral ◽  
Sabina G. Astete ◽  
Craig R. Cohen ◽  
Eduardo P. C. Rocha ◽  
Patricia A. Totten
Keyword(s):  
Reproductive Tract ◽  
Natural Infection ◽  
Mycoplasma Genitalium ◽  
Infected Woman ◽  
Expression Site ◽  
Tract Disease ◽  
Adhesin Protein ◽  
Chromosomal Sequences

ABSTRACT Mycoplasma genitalium is associated with reproductive tract disease in women and may persist in the lower genital tract for months, potentially increasing the risk of upper tract infection and transmission to uninfected partners. Despite its exceptionally small genome (580 kb), approximately 4% is composed of repeated elements known as MgPar sequences (MgPa repeats) based on their homology to the mgpB gene that encodes the immunodominant MgPa adhesin protein. The presence of these MgPar sequences, as well as mgpB variability between M. genitalium strains, suggests that mgpB and MgPar sequences recombine to produce variant MgPa proteins. To examine the extent and generation of diversity within single strains of the organism, we examined mgpB variation within M. genitalium strain G-37 and observed sequence heterogeneity that could be explained by recombination between the mgpB expression site and putative donor MgPar sequences. Similarly, we analyzed mgpB sequences from cervical specimens from a persistently infected woman (21 months) and identified 17 different mgpB variants within a single infecting M. genitalium strain, confirming that mgpB heterogeneity occurs over the course of a natural infection. These observations support the hypothesis that recombination occurs between the mgpB gene and MgPar sequences and that the resulting antigenically distinct MgPa variants may contribute to immune evasion and persistence of infection.

scholarly journals Synthesis and antibacterial activity of 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a] azepin-1-ium bromides and aryl-(4-R1-phenyl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulen-1-ylmethyl)-amines

2021 ◽  
pp. 51-57
Author(s):  
Nataliya Demchenko ◽  
Zinaida Suvorova ◽  
Yuliia Fedchenkova ◽  
Tamara Shpychak ◽  
Oleh Shpychak ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Properties ◽  
Antimicrobial Drugs ◽  
Reference Drug ◽  
Gram Negative ◽  
In Vivo Experiments ◽  
Yeast Fungi ◽  
Methods Of Synthesis ◽  
Bacteria And Fungi

The aim of this work is to develop methods of synthesis of 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromides and aryl-(4-R1-phenyl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulen-1-ylmethyl)-amines and to study their antimicrobial activity against strains of gram-positive and gram-negative bacteria as well as yeast fungi. Materials and methods. 1Н NMR spectra were recorded on Bruker 400 spectrometer operating at frequency of 400 MHz. Antimicrobial activity of the compounds synthesized was evaluated by their minimum inhibitory concentration (MIC) values. Results and discussion. The interaction of 3-arylaminomethyl-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepines with substituted phenacyl bromides produced novel 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromides. The latter when refluxed in 10 % solution of NaOH gave aryl-(4-R1-phenyl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulen-1-ylmethyl)-amines. The study of antimicrobial activity of the compounds obtained allowed to find derivatives which are active against С. albicans and S. aureus strains. Among the compounds tested 3-[(41-bromophenylamino)-methyl]-1-[2-(4-methoxyphenyl)-2-oxoethyl]-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromide 5cd appeared to be more active than the reference drug Cefixime and displayed close antimicrobial activity as the antibiotic Linezolid. Conclusions. It was found out that derivatives of 3-arylaminomethyl-1-(2-oxo-2-arylethyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-1-ium bromides display broad spectrum of antimicrobial activity and are able to inhibit growth of both bacteria and fungi. S. aureus and C. albicans turned out to be the most sensitive strains to the compounds tested, MIC was in the range of 6.2-25.0 mg/mL. Gram-negative strains of microorganisms were less sensitive to the compounds evaluated and 5fа was the most active derivative displaying antimicrobial activity at the concentration of 50.0 mg/mL. Antimicrobial activity of triazoloazepinium bromide derivatives was similar to that one of Linezolid and Fluconazole reference drugs and more pronounced than the activity of Cefixime. Hence, the data gathered evidence the feasibility of further study of the antimicrobial properties of the most active compounds in in vivo experiments aiming at assessment of the prospects for the creation of new effective and safe antimicrobial drugs based on them

scholarly journals Association of Uterine and Salpingeal Fibrosis with Chlamydial Hsp60 and Hsp10 Antigen-Specific Antibodies in Chlamydia-Infected Koalas

2005 ◽  
Vol 12 (5) ◽  
pp. 632-639 ◽  
Author(s):  
Damien P. Higgins ◽  
Susan Hemsley ◽  
Paul J. Canfield
Keyword(s):  
Active Component ◽  
Chlamydia Pneumoniae ◽  
Reproductive Tract ◽  
Epidemiological Studies ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Female ◽  
Tubal Infertility ◽  
Tubal Occlusion ◽  
Chlamydia Pecorum ◽  
Tract Disease

ABSTRACT Infection by Chlamydia pneumoniae or Chlamydia pecorum commonly causes chronic, fibrotic disease of the urogenital tracts of female koalas. Studies of humans have associated titers of serum immunoglobulin G (IgG) against chlamydial hsp60 and hsp10 antigens with chronic infection, salpingeal fibrosis, and tubal infertility. To determine whether a similar relationship exists in Chlamydia-infected koalas, samples were collected opportunistically from 34 wild female koalas and examined by gross pathology and histopathology, PCR, and immunohistochemistry for Chlamydia spp. and enzyme-linked immunosorbent assay for serological responses to chlamydial hsp10 and hsp60 antigens. Greater anti-hsp titers occurred in Chlamydia-infected koalas with fibrous occlusion of the uterus or uterine tube than in other Chlamydia-infected koalas (for hsp10 IgG, P = 0.005; for hsp60 IgG, P = 0.001; for hsp10 IgA, P = 0.04; for hsp60 IgA, P = 0.09). However, as in humans, some koalas with tubal occlusion had low titers. Among Chlamydia-infected koalas with tubal occlusion, those with low titers were more likely to have an active component to their ongoing uterine or salpingeal inflammation (P = 0.007), such that the assay predicted, with 79% sensitivity and 92% specificity, tubal occlusion where an active component of inflammation was absent. Findings of this study permit advancement of clinical and epidemiological studies of host-pathogen-environment interactions and pose intriguing questions regarding the significance of the Th1/Th2 paradigm and antigen-presenting and inflammation-regulating capabilities of uterine epithelial cells and the roles of latency and reactivation of chlamydial infections in pathogenesis of upper reproductive tract disease of koalas.

scholarly journals Comparative Anti-malarial and Toxicological Properties of the Stem Bark ‎Extracts of Nauclea latifolia and Terminalia glaucescens Against ‎Plasmodium berghei-infected Mice

2020 ◽  
Vol 14 (1) ◽  
pp. 9-18
Author(s):  
Eustace Bonghan Berinyuy ◽  
◽  
Mann Abdullahi ◽  
Adamu Yusuf Kabiru ◽  
Emmanuel Olofu Ogbadoyi ◽  
...  
Keyword(s):  
Body Weight ◽  
Plasmodium Berghei ◽  
Lethal Dose ◽  
Stem Bark ◽  
Positive Control ◽  
Negative Control ◽  
Significant Loss ◽  
The Body ◽  
Nauclea Latifolia

Background: Anti-plasmodial activities of the methanol stem bark extracts of Nauclea latifolia, and Terminalia glaucescens were investigated in mice infected with Plasmodium berghei. Methods: A total of 24 Plasmodium berghei infected (P. berghei infected) mice were divided into 8 groups of 3 each. Groups A-F were given 100, 300 or 500 mg/kg of either extracts. Groups G and H received 2 mL normal saline (negative control) and 5 mg/kg of chloroquine (positive control), respectively. The drugs and extracts were administered orally once daily for five days. Results: Alkaloids and flavonoids were the most and abundant metabolites in the extracts, respectively. The extract of Nauclea latifolia (N. latifolia) and Terminalia glaucescens (T. glauscecens) had Median Lethal Dose LD50 of >5000 mg/kg and 3808 mg/kg, respectively. In vivo anti-plasmodial studies revealed that the highest suppression (66.79% and 65.37%) and mean survival days (27.67±1.45 and 30.33±0.33) were recorded for the groups treated with 500 mg/kg N. latifolia or T. glaucescens, respectively. The infected but untreated groups survived only for 9.33±0.88 days while chloroquine treated groups lived for 31.33±0.88 days. The body weight and Packed Cell Volume (PCV) of rats treated with 500 mg/kg. N. latifolia or T. glaucescens significantly increased (P<0.05) compared to those in the infected but untreated groups. There was a significant loss (P<0.05) in body weight and PCV of the mice treated with 100 mg/kg of T. glaucescens compared to those in other treated groups. Conclusion: The extracts exhibited anti-plasmodial activities in mice, therefore, they may be considered potential candidates for new anti-malarial agents.

scholarly journals Effects of Preservatives Added in Cookies on Intestinal Bacteria

2021 ◽  
pp. 278-284
Author(s):  
G. S. Sutharshan ◽  
N. P. Muralidharan
Keyword(s):  
Antimicrobial Activity ◽  
Oral Cavity ◽  
Intestinal Bacteria ◽  
The Body ◽  
Food Spoilage ◽  
Sterile Saline ◽  
Bacteria And Fungi ◽  
Growth Of Fungi ◽  
Colony Counter ◽  
Growth Of Bacteria

Introduction: An essential thing for human survival is food which provides nutritional support for the body or for pleasure. All the food used today has some preservatives, except our own garden plants. Preservatives prevent food spoilage from microorganisms but it will inhibit the growth of bacteria and fungi. Antimicrobial preservatives are the preservatives which inhibit the growth of fungi and bacteria. Methods of preserving foods have been used for centuries and include natural techniques such as smoking fish and meat as well as adding salts. Aim: The main aim of the study is to find the effects of preservatives added in cookies on intestinal bacteria. Materials and Method: Take a sample of 10 biscuits. Crush and mix 10 gms in 10 ml of sterile saline. soak for 30 mins and centrifuge and take the supernatant. Transfer 1 ml to each tube and add the selected organisms (lactobacilli). Add 10 microlitre of the selected organism (lactobacilli) to the supernatant. Hold for 30 mins and transfer 10 microlitre to BHI and count the CFU after incubation for 12 hours. Results and Discussion:  After 12 hrs of incubation, colonies are formed. Using colony counter app colonies are counted. Biscuits 4 showed the highest growth of colonies of 797. The control of the bacteria shows confluence growth where the unlimited colonies are formed. This indicates the presence of antimicrobial activity on preservatives added in biscuits. This antimicrobial activity affects the health of the oral cavity and intestine. Conclusion: From the above study, it is evident that the antimicrobial activity of preservatives that are added in biscuits could affect the health of oral cavity and intestine.

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