scholarly journals Light Modulates Important Pathogenic Determinants and Virulence in Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus ESKAPE Pathogens

2020 ◽  
Author(s):  
M. R. Tuttobene ◽  
J. F. Pérez ◽  
E. Pavesi ◽  
B. Perez Mora ◽  
D. Biancotti ◽  
...  

Light sensing has been extensively characterized in the human pathogen Acinetobacter baumannii at environmental temperatures. However, the influence of light on the physiology and pathogenicity of human bacterial pathogens at temperatures found in warm-blooded hosts is still poorly understand. In this work, we show that ESKAPE priority pathogens, such as Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter spp., which have been recognized by the WHO and the CDC as critical, can also sense and respond to light at temperatures found in human hosts. Most interestingly, in these pathogens light modulates important pathogenicity determinants as well as virulence in an epithelial infection model, which could have implications in human infections. In fact, we found that alpha-toxin-dependent hemolysis, motility and growth under iron deprived conditions are modulated by light in S. aureus. Light also regulates persistence, metabolism and the ability to kill competitors, in some of these microorganisms. Finally, light exerts a profound effect on the virulence of these pathogens in an epithelial infection model, though the response is not the same in the different species: virulence was enhanced by light in A. baumannii and S. aureus, while in A. nosocomialis and P. aeruginosa it was reduced. Neither the BlsA photoreceptor nor the type VI secretion system (T6SS) are involved in virulence modulation by light in A. baumannii. Overall, this fundamental knowledge highlights the potential use of light to control pathogen's virulence, either directly or by manipulating the light regulatory switch toward the lowest virulence/persistence configuration. IMPORTANCE Pathogenic bacteria are microorganisms capable of producing disease. Dangerous bacterial pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii are responsible for serious intrahospital and community infections in humans. Therapeutics is often complicated due to resistance to multiple antibiotics, rendering them ineffective. In this work, we show that these pathogens sense natural light and respond to it by modulating aspects related to their ability to cause disease: in the presence of light some of them become more aggressive while others show an opposite response. Overall, we provide new understanding on the behavior of these pathogens, which could contribute to control infections caused by them. Since the response is distributed in diverse pathogens, this notion could prove a general concept.

2014 ◽  
Vol 58 (9) ◽  
pp. 5363-5371 ◽  
Author(s):  
Fany Reffuveille ◽  
César de la Fuente-Núñez ◽  
Sarah Mansour ◽  
Robert E. W. Hancock

ABSTRACTBiofilm-related infections account for at least 65% of all human infections, but there are no available antimicrobials that specifically target biofilms. Their elimination by available treatments is inefficient since biofilm cells are between 10- and 1,000-fold more resistant to conventional antibiotics than planktonic cells. Here we describe the synergistic interactions, with different classes of antibiotics, of a recently characterized antibiofilm peptide, 1018, to potently prevent and eradicate bacterial biofilms formed by multidrug-resistant ESKAPE (Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacterspecies) pathogens. Combinations of peptide 1018 and the antibiotic ceftazidime, ciprofloxacin, imipenem, or tobramycin were synergistic in 50% of assessments and decreased by 2- to 64-fold the concentration of antibiotic required to treat biofilms formed byPseudomonas aeruginosa,Escherichia coli,Acinetobacter baumannii,Klebsiella pneumoniae,Salmonella enterica, and methicillin-resistantStaphylococcus aureus. Furthermore, in flow cell biofilm studies, combinations of low, subinhibitory levels of the peptide (0.8 μg/ml) and ciprofloxacin (40 ng/ml) decreased dispersal and triggered cell death in matureP. aeruginosabiofilms. In addition, short-term treatments with the peptide in combination with ciprofloxacin prevented biofilm formation and reducedP. aeruginosaPA14 preexisting biofilms. PCR studies indicated that the peptide suppressed the expression of various antibiotic targets in biofilm cells. Thus, treatment with the peptide represents a novel strategy to potentiate antibiotic activity against biofilms formed by multidrug-resistant pathogens.


2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Hussein A Kadhum ◽  
Thualfakar H Hasan2

The study involved the selection of two isolates from Bacillus subtilis to investigate their inhibitory activity against some bacterial pathogens. B sub-bacteria were found to have a broad spectrum against test bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. They were about 23-30 mm and less against Klebsiella sp. The sensitivity of some antibodies was tested on the test samples. The results showed that the inhibitory ability of bacterial growth in the test samples using B. subtilis extract was more effective than the antibiotics used.


2005 ◽  
Vol 187 (2) ◽  
pp. 554-566 ◽  
Author(s):  
Lauren M. Mashburn ◽  
Amy M. Jett ◽  
Darrin R. Akins ◽  
Marvin Whiteley

ABSTRACT Pseudomonas aeruginosa is a gram-negative opportunistic human pathogen often infecting the lungs of individuals with the heritable disease cystic fibrosis and the peritoneum of individuals undergoing continuous ambulatory peritoneal dialysis. Often these infections are not caused by colonization with P. aeruginosa alone but instead by a consortium of pathogenic bacteria. Little is known about growth and persistence of P. aeruginosa in vivo, and less is known about the impact of coinfecting bacteria on P. aeruginosa pathogenesis and physiology. In this study, a rat dialysis membrane peritoneal model was used to evaluate the in vivo transcriptome of P. aeruginosa in monoculture and in coculture with Staphylococcus aureus. Monoculture results indicate that approximately 5% of all P. aeruginosa genes are differentially regulated during growth in vivo compared to in vitro controls. Included in this analysis are genes important for iron acquisition and growth in low-oxygen environments. The presence of S. aureus caused decreased transcription of P. aeruginosa iron-regulated genes during in vivo coculture, indicating that the presence of S. aureus increases usable iron for P. aeruginosa in this environment. We propose a model where P. aeruginosa lyses S. aureus and uses released iron for growth in low-iron environments.


2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Mojgan Sabet ◽  
Ziad Tarazi ◽  
David C. Griffith

ABSTRACTWe have evaluated the activity of meropenem-vaborbactam against clinical isolates ofPseudomonas aeruginosaandAcinetobacter baumanniiin a neutropenic mouse thigh infection model. Data show that meropenem-vaborbactam regimens equivalent to 3-h infusions every 8 h with 2 g meropenem and 2 g vaborbactam produced bacterial killing against strains with MICs of 2 to 16 mg/liter and suggests that this combination may have utility in the treatment of infections caused byP. aeruginosaandA. baumannii.


Author(s):  
Mirela C. M. Prates ◽  
Edwin Tamashiro ◽  
José L. Proenca-Modena ◽  
Miriã F. Criado ◽  
Tamara H. Saturno ◽  
...  

We sought to investigate the prevalence of potentially pathogenic bacteria in secretions and tonsillar tissues of children with chronic adenotonsillitis hypertrophy compared to controls. Prospective case-control study comparing patients between 2 and 12 years old who underwent adenotonsillectomy due to chronic adenotonsillar hypertrophy to children without disease. We compared detection of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Pseudomonas aeruginosa, and Moraxella catarrhalis by real-time PCR in palatine tonsils, adenoids, and nasopharyngeal washes obtained from 37 children with and 14 without adenotonsillar hypertrophy. We found high frequency (>50%) of Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa in both groups of patients. Although different sampling sites can be infected with more than one bacterium and some bacteria can be detected in different tissues in the same patient, adenoids, palatine tonsils, and nasopharyngeal washes were not uniformly infected by the same bacteria. Adenoids and palatine tonsils of patients with severe adenotonsillar hypertrophy had higher rates of bacterial coinfection. There was good correlation of detection of Moraxella catarrhalis in different sampling sites in patients with more severe tonsillar hypertrophy, suggesting that Moraxella catarrhalis may be associated with the development of more severe hypertrophy, that inflammatory conditions favor colonization by this agent. Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis are frequently detected in palatine tonsils, adenoids, and nasopharyngeal washes in children. Simultaneous detection of Moraxella catarrhalis in adenoids, palatine tonsils, and nasopharyngeal washes was correlated with more severe tonsillar hypertrophy.


2018 ◽  
Vol 63 (2) ◽  
pp. e01040-18 ◽  
Author(s):  
Sean M. Stainton ◽  
Marguerite L. Monogue ◽  
Masakatsu Tsuji ◽  
Yoshinori Yamano ◽  
Roger Echols ◽  
...  

ABSTRACT Herein, we evaluated sustainability of humanized exposures of cefiderocol in vivo over 72 h against pathogens with cefiderocol MICs of 0.5 to 16 μg/ml in the neutropenic murine thigh model. In Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae displaying MICs of 0.5 to 8 μg/ml (n = 11), sustained kill was observed at 72 h among 9 isolates. Postexposure MICs revealed a single 2-dilution increase in one animal compared with controls (1/54 samples, 1.8%) at 72 h. Adaptive resistance during therapy was not observed.


Author(s):  
I. I. Myrko ◽  
T. I. Chaban ◽  
V. V. Ogurtsov ◽  
V. S. Matiychuk

Мета роботи. Здійснити синтез деяких нових піразолзаміщених 7H-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазинів та провести дослідження антимікробних властивостей синтезованих сполук. Матеріали і методи. Органічний синтез, ЯМР-спектроскопія, елементний аналіз, фармакологічний скринінг. Результати й обговорення. У результаті взаємодії eтил (2Z)-хлоро(фенілгідразоно)ацетатів з ацетилацетоном було отримано етил 4-ацетил-5-метил-1-феніл-1H-піразол-3-карбоксилати. Зазначені сполуки піддали бромуванню, що дозволило одержати цільові бромкетони. Синтезовані на даній стадії етил 1-арил-4-(бромацетил)-5-метил-1Н-піразол-3-карбоксилати було введено у взаємодію з 4-аміно-5-арил(гетарил)-2,4-дигідро-3Н-1,2,4-триазол-3-тіонами з подальшим формуванням 1,3,4-тіадіазольного циклу та отриманням відповідних етил 1-арил-4-{3-арил(гетарил)-7H-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазин-6-іл)}-5-метил-1H-піразол-3-карбоксилатів. Структура синтезованих сполук підтверджена даними елементного аналізу та ЯМР спектроскопією. В рамках міжнародного проекту "The Community for Antimicrobial Drug Discovery" (CO-ADD) за підтримки Wellcome Trust (Великобританія) і університету Квінсленда (Австралія) для синтезованих сполук здійснено скринінг антимікробної активності. Як тестові мікроорганізми використовували п'ять штамів бактерій: Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 700603, Acinetobacter baumannii ATCC 19606, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 43300 та двох штамів грибків: Candida albicans ATCC 90028 і Cryptococcus neoformans ATCC 208821. Встановлено, що досліджувані сполуки виявляють різноманітну дію, від практично повної її відсутності до виразного антимікробного ефекту. Висновки. Здійснено синтез 12 нових етил 1-арил-4-{3-арил(гетарил)-7H-[1,2,4]триазоло[3,4-b][1,3,4]тіадіазин-6-іл)}-5-метил-1H-піразол-3-карбоксилатів. Зазначені речовини отримані шляхом взаємодії відповідних етил 1-арил-4-(бромацетил)-5-метил-1Н-піразол-3-карбоксилатів з 4-аміно-5-арил(гетарил)-2,4-дигідро-3Н-1,2,4-триазол-3-тіонами. Дослідження антимікробної активності синтезованих сполук демонструють потенціал пошуку антимікробних агентів серед зазначеного класу сполук.


Author(s):  
Guillaume Ménard ◽  
Astrid Rouillon ◽  
Gevorg Ghukasyan ◽  
Mathieu Emily ◽  
Brice Felden ◽  
...  

Small regulatory RNAs (sRNAs) are key players in bacterial regulatory networks. Monitoring their expression inside living colonized or infected organisms is essential for identifying sRNA functions, but few studies have looked at sRNA expression during host infection with bacterial pathogens. Insufficient in vivo studies monitoring sRNA expression attest to the difficulties in collecting such data, we therefore developed a non-mammalian infection model using larval Galleria mellonella to analyze the roles of Staphylococcus aureus sRNAs during larval infection and to quickly determine possible sRNA involvement in staphylococcal virulence before proceeding to more complicated animal testing. We began by using the model to test infected larvae for immunohistochemical evidence of infection as well as host inflammatory responses over time. To monitor sRNA expression during infection, total RNAs were extracted from the larvae and invading bacteria at different time points. The expression profiles of the tested sRNAs were distinct and they fluctuated over time, with expression of both sprD and sprC increased during infection and associated with mortality, while rnaIII expression remained barely detectable over time. A strong correlation was observed between sprD expression and the mortality. To confirm these results, we used sRNA-knockout mutants to investigate sRNA involvement in Staphylococcus aureus pathogenesis, finding that the decrease in death rates is delayed when either sprD or sprC was lacking. These results demonstrate the relevance of this G. mellonella model for investigating the role of sRNAs as transcriptional regulators involved in staphylococcal virulence. This insect model provides a fast and easy method for monitoring sRNA (and mRNA) participation in S. aureus pathogenesis, and can also be used for other human bacterial pathogens.


2018 ◽  
Vol 7 (2) ◽  
pp. 125-139
Author(s):  
Thais Nogueira Gonzaga ◽  
Dora Inés Kozusny-Andreani

Nesta pesquisa objetivou-se avaliar a viabilidade técnica da aplicação de ozônio como bactericida e fungicida em amostras de resíduos de serviços de saúde potencialmente infectantes. Foram determinados os     micro-organismos presentes nos resíduos gerados em um hospital particular. Para realização das análises microbiológicas e o tratamento com ozônio o material foi particulado e homogeneizado. As análises microbiológicas foram realizadas antes e após a ozonização.Para os testes de desinfecção foram retirados 10,0g de amostra que foi submetida à ozonização por 5, 10, 15, 20 e 25 minutos com doses de 140,0; 280,0; 420,0; 560,0 e 700,0mg L-1 de ozônio, respectivamente. Verificou-se presença de mesófilos totais, coliformes totais e termotolerantes, Escherichia coli, Pseudomonas aeruginosa, Proteus spp., Staphylococcus aureus, Staphylococcus spp, Candida albicans e Rhizopus spp. O ozônio foi eficiente para eliminação de todos os micro-organismos em 20 minutos; nos primeiros cinco minutos de exposição ao gás verificou-se redução superior a 98%.Palavras-chave: Bactérias patogênicas. Fungos. Ozonização. USING OZONE GAS FOR DISINFECTION OF SOLID WASTE FROM HEALTH CARE SERVICES ABSTRACT: The aim of this research was to evaluate the technical viability of the application of ozone as bactericide and fungicide in samples of potentially infectious health services residues. The microorganisms present in the waste generated in a private hospital were determined. The material was particulated and homogenized to perform the microbiological analysis and to undergo ozone treatment. Microbiological analysis was performed before and after ozonization. For the disinfection tests, 10.0g of sample were removed and submitted to ozonization for 5, 10, 15, 20 and 25 minutes with 140,0; 280,0; 420,0; 560,0 and 700,0mg doses of L-1 of ozone, respectively. It was verified the presence of total mesophiles, total and thermotolerant coliforms, Escherichia coli, Pseudomonas aeruginosa, Proteus spp., Staphylococcus aureus, Staphylococcus spp, Candida albicans and Rhizopus spp. Ozone was efficient while eliminating all microorganisms in 20 minutes; in the first five minutes of gas exposure, the reduction was greater than 98%.Keywords: Pathogenic bacteria. Fungi. Ozonization.


Sign in / Sign up

Export Citation Format

Share Document