Opportunistic Pathogen
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2021 ◽  
Vol 12 (1) ◽  
Jessie MacAlpine ◽  
Martin Daniel-Ivad ◽  
Zhongle Liu ◽  
Junko Yano ◽  
Nicole M. Revie ◽  

AbstractThe fungus Candida albicans is an opportunistic pathogen that can exploit imbalances in microbiome composition to invade its human host, causing pathologies ranging from vaginal candidiasis to fungal sepsis. Bacteria of the genus Lactobacillus are colonizers of human mucosa and can produce compounds with bioactivity against C. albicans. Here, we show that some Lactobacillus species produce a small molecule under laboratory conditions that blocks the C. albicans yeast-to-filament transition, an important virulence trait. It remains unexplored whether the compound is produced in the context of the human host. Bioassay-guided fractionation of Lactobacillus-conditioned medium linked this activity to 1-acetyl-β-carboline (1-ABC). We use genetic approaches to show that filamentation inhibition by 1-ABC requires Yak1, a DYRK1-family kinase. Additional biochemical characterization of structurally related 1-ethoxycarbonyl-β-carboline confirms that it inhibits Yak1 and blocks C. albicans biofilm formation. Thus, our findings reveal Lactobacillus-produced 1-ABC can prevent the yeast-to-filament transition in C. albicans through inhibition of Yak1.

Danielle A. Nicklas ◽  
Emily C. Maggioncalda ◽  
Elizabeth Story-Roller ◽  
Benjamin Eichelman ◽  
Chavis Tabor ◽  

The incidence of nontuberculous mycobacterial diseases in the US is rising and has surpassed tuberculosis. Most notable among the nontuberculous mycobacteria is Mycobacteroides abscessus , an emerging environmental opportunistic pathogen capable of causing chronic infections. M. abscessus disease is difficult to treat and the current treatment recommendations include repurposed antibiotics, several of which are associated with undesirable side effects. In this study, we have evaluated the activity of omadacycline, a new tetracycline derivative, against M. abscessus using in vitro and in vivo approaches. Omadacycline exhibited an MIC 90 of 0.5 μg/ml against a panel of 32 contemporary M. abscessus clinical isolates several of which were resistant to antibiotics that are commonly used for treatment of M. abscessus disease. Omadacycline when combined with clarithromycin, azithromycin, cefdinir, rifabutin or linezolid also exhibited synergism against several M. abscessus strains and did not exhibit antagonism when combined with an additional nine antibiotics also commonly considered to treat M. abscessus disease. Concentration-dependent activity of omadacycline was observed in time-kill assessments. Efficacy of omadacycline was evaluated in a mouse model of lung infection against four M. abscessus strains. A dose equivalent to the 300 mg standard oral human dose was used. Compared to the untreated control group, within four weeks of treatment, 1 to 3 log 10 fewer M. abscessus colony forming units were observed in the lungs of mice treated with omadacycline. Treatment outcome was biphasic, with bactericidal activity observed after the first two weeks of treatment against all four M. abscessus strains.

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6283
Hong-Fei Li ◽  
Meng-Ru Wang ◽  
Lin-Yue Tian ◽  
Zheng-Jun Li

Vibrio alginolyticus is a halophilic organism usually found in marine environments. It has attracted attention as an opportunistic pathogen of aquatic animals and humans, but there are very few reports on polyhydroxyalkanoate (PHA) production using V. alginolyticus as the host. In this study, two V. alginolyticus strains, LHF01 and LHF02, isolated from water samples collected from salt fields were found to produce poly(3-hydroxybutyrate) (PHB) from a variety of sugars and organic acids. Glycerol was the best carbon source and yielded the highest PHB titer in both strains. Further optimization of the NaCl concentration and culture temperature improved the PHB titer from 1.87 to 5.08 g/L in V. alginolyticus LHF01. In addition, the use of propionate as a secondary carbon source resulted in the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). V. alginolyticus LHF01 may be a promising host for PHA production using cheap waste glycerol from biodiesel refining.

Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1258
Elisabetta Buommino ◽  
Simona De Marino ◽  
Martina Sciarretta ◽  
Marialuisa Piccolo ◽  
Carmen Festa ◽  

Staphylococcusaureus is an important opportunistic pathogen that causes many infections in humans and animals. The inappropriate use of antibiotics has favored the diffusion of methicillin-resistant S. aureus (MRSA), nullifying the efforts undertaken in the discovery of antimicrobial agents. Oxadiazole heterocycles represent privileged scaffolds for the development of new drugs because of their unique bioisosteric properties, easy synthesis, and therapeutic potential. A vast number of oxadiazole-containing derivatives have been discovered as potent antibacterial agents against multidrug-resistant MRSA strains. Here, we investigate the ability of a new library of oxadiazoles to contrast the growth of Gram-positive and Gram-negative strains. The strongest antimicrobial activity was obtained with compounds 3 (4 µM) and 12 (2 µM). Compound 12, selected for further evaluation, was found to be noncytotoxic on the HaCaT cell line up to 25 µM, bactericidal, and was able to improve the activity of oxacillin against the MRSA. The highest synergistic interaction was obtained with the combination values of 0.78 μM for compound 12, and 0.06 μg/mL for oxacillin. The FIC index value of 0.396 confirms the synergistic effect of compound 12 and oxacillin. MRSA treatment with compound 12 reduced the expression of genes included in the mec operon. In conclusion, 12 inhibited the growth of the MRSA and restored the activity of oxacillin, thus resulting in a promising compound in the treatment of MRSA infection.

2021 ◽  
William Y. Harvey ◽  
Cynthia Gagné-Thivierge ◽  
Sepideh Fakari ◽  
Jean Barbeau ◽  
Steve Charette ◽  

The bacterium Pseudomonas aeruginosa is an opportunistic pathogen in certain organisms, including humans, but can also survive and proliferate in natural and engineered water systems. Microfluidic technology can address hydrodynamic questions related to bacterial contamination of water flow systems and infrastructure. In this work, a microfluidic approach was devised to study the effect of shear stresses on biofilms from a dental unit waterline (DUWL)-isolated P. aeruginosa strain, PPF-1. During application of relevant shear stress levels to DUWLs, the response of the PPF-1 biofilm was observed and compared to a clinical P. aeruginosa reference strain, PAO1. The response measurements were repeated for biofilms exposed to additional Mg2+ ions. Using a microfluidic approach to transforming optical density maps into three-dimensional images, we applied computational fluid dynamics simulations and determined the critical shear stresses for biofilm sloughing. In the absence of Mg2+, PPF-1 biofilms showed weaker attachment than PAO1 biofilms, resulting in continuous slough/regrowth cycles triggered by applied shear stresses of 1.42 +/- 0.32 Pa. Introducing Mg2+ into the PPF-1 biofilm culture medium seemed to place the biofilm into a viscoplastic mechanical state, thereby increasing mechanical stability, which resulted in elevated tolerances to shear stresses up to a critical value of 5.43 +/- 1.52 Pa. This resulted in a propensity for less frequent but more catastrophic sloughing events like that observed for the PAO1 reference strain. This suggests that in a low ionic environment, biofilms from the PPF-1 strain can result in higher and more continuous ejection of biofilm materials, possibly leading to increased downstream colonization of engineered flow systems.

Ranjana Rohilla ◽  
Dimple Raina ◽  
Malvika Singh ◽  
Ajay Kumar Pandita ◽  
Shiwang Patwal

Background and Objectives: Sphingomonas paucimobilis is an opportunistic pathogen and was rarely encountered in clin- ical specimens previously. This study aimed to investigate the clinical features, associated co-morbidities, and antimicrobial susceptibility patterns of S. paucimobilis infection in a tertiary hospital in Uttarakhand. Materials and Methods: S. paucimobilis isolates cultured from various sections of hospital and OPDs were identified and an- alyzed for their antibiograms in the microbiology laboratory for a duration of one year from January 2020 to December 2020. Results: S. paucimobilis was isolated from 49 samples (0.01%) out of 3792 samples processed in VITEK 2 Compact auto- mated ID/AST instrument. The maximum number of isolates were obtained from urine samples (31%), followed by blood (24%). Septicemia (41%), meningitis (17%), lower respiratory tract infections and ventilator associated pneumonia (14%) constituted a major portion of infections caused by this organism. Diabetes mellitus (22%) and steroid usage (16%) were major associated co-morbid conditions. Third and Fourth generation cephalosporins like ceftriaxone (81%) and cefepime (86%) were found to be the most susceptible drugs whereas 61% of isolates were resistant to colistin. Conclusion: This organism is an up-and-coming pathogen and should not be simply labeled as a contaminant. Although the organism is not grossly virulent and still might not be associated with serious life-threatening infections; however their evolving resistance patterns and increased spectrum of infections should be seriously taken into account.

Fatemeh Esmaeilzadeh ◽  
Shirin Mahmoodi

Background: As an opportunistic pathogen, Pseudomonas aeruginosa causes many different hazardous infections. The high mortality rate resulting from infection with this antibiotic-resistant pathogen has made it a major challenge in clinical treatment; it has been listed as the most harmful bacterium to humans by the WHO. So far, no vaccine has been approved for P. aeruginosa. Objective: Infections performed by bacterial attachment and colonization with type IV pili (T4P), known as the most essential adhesive vital for adhesion, while pilQ is necessary for the biogenesis of T4P, also outer membrane proteins of a pathogen is also effective in stimulating the immune system; in this regard, pilQ, OprF, and OprI, are excellent candidate antigens for production of an effective vaccine against P. aeruginosa. Methods: In this research, various bioinformatics methods were employed in order to design a new multi-epitope peptide vaccine versus P. aeruginosa. Since T CD4+ cell immunity is important in eradicating P. aeruginosa, OprF, OprI, and pilQ antigens were analyzed to determineHelper T cell Lymphocyte (HTL) epitopes by many different immunoinformatics servers. One of the receptor agonists 2 (TLR2), a segment of the Por B protein from Neisseria meningitides was used as an adjuvant in order to stimulate an effective cellular immune response, and suitable linkers were used to connect all the above mentioned parts. In the vaccine construct, linear B cell epitopes were also identified. Results: Conforming the bioinformatics forecasts, the designed vaccine possesses high antigenicity and is not allergen. Conclusion: In this regard, the designed vaccine candidate is strongly believed to possess the potential of inducing cellular and humoral immunity against P. aeruginosa.

2021 ◽  
Xianggui Yang ◽  
Zhenguo Wang ◽  
Xuejing Yu ◽  
Yuanxiu Zhong ◽  
Fuying Wang ◽  

Abstract Background: Enterobacter cloacae (EC) is a commonly occurring opportunistic pathogen and is responsible for causing various infections in humans. Owing to its inducible chromosomal AmpC β-lactamase (AmpC), EC is inherently resistant to the 1st- and 2nd- generation cephalosporins. However, whether β-lactams antibiotics enhance EC resistance remains unclear.Results: In this study, we found that subinhibitory concentrations (SICs) of cefazolin (CFZ) and imipenem (IMP) are able to advance the expression of AmpC and improve its resistance towards β - lactams through NagZ in EC clinical isolate. Our work indicate that AmpC manifested a substantial upregulation in EC in response to SICs of CFZ and IMP. In nagZ knockout EC (ΔnagZ), we found that the resistance to β - lactam antibiotics was rather weakened and the effect of CFZ and IMP on induction of AmpC was completely abrogated. Ectopic expression of NagZ can rescue the induction effect of CFZ and IMP on AmpC and enhance resistance in ΔnagZ. More importantly, CFZ and IMP have the potential to bring about the target genes expressions of AmpR in a NagZ-dependent manner.Conclusions: Our findings show that NagZ is a critical determinant for CFZ and IMP to promote AmpC expression and improve resistance and that CFZ and IMP should be used with caution since they may aggravate EC resistance. At the same time, this study further improves our understanding of resistance mechanisms in EC.

2021 ◽  
Yuma Shisaka ◽  
Erika Sakakibara ◽  
Kazuto Suzuki ◽  
Joshua Kyle Stanfield ◽  
Hiroki Onoda ◽  

Tetraphenylporphyrin (TPP) is a synthetic porphyrin whose properties can be readily modified, endowing it with significant benefits over naturally occurring porphyrins. Yet, their insolubility in water and/or steric bulk have rendered them incompatible with biological systems. Herein, we report the first example of a native biomolecule capturing TPP as well as its derivatives. The haemoprotein HasA, secreted by certain pathogens to scavenge haem from their hosts, can capture various metal- and meso-substituted TPPs. The rapid crystallisation of TPP derivatives captured by HasA revealed the binding mode of TPP at excellent resolutions. A single-site mutation (L85A) of HasA enlarged the binding pocket, allowing the incorporation of a bulkier derivative of TPP. HasA binding TPP derivatives was also demonstrated to inhibit proliferation of the opportunistic pathogen Pseudomonas aeruginosa. This study not only represents a simple method for the complexation of TPP derivatives with a native protein, but also opens the door for the future use of TPP derivatives as biological tools.

2021 ◽  
Vol 21 (1) ◽  
Lirong Bao ◽  
Cheng Zhang ◽  
Jinglu Lyu ◽  
Caixia Yan ◽  
Ranran Cao ◽  

Abstract Background Fusobacterium nucleatum (F. n) is an important opportunistic pathogen causing oral and gastrointestinal disease. Faecalibacterium prausnitzii (F. p) is a next-generation probiotic and could serve as a biomarker of gut eubiosis/dysbiosis to some extent. Alterations in the human oral and gut microbiomes are associated with viral respiratory infection. The aim of this study was to characterise the oral and fecal bacterial biomarker (i.e., F. n and F. p) in COVID-19 patients by qPCR and investigate the pharyngeal microbiome of COVID-19 patients through metagenomic next-generation sequencing (mNGS). Results Pharyngeal F. n was significantly increased in COVID-19 patients, and it was higher in male than female patients. Increased abundance of pharyngeal F. n was associated with a higher risk of a positive SARS-CoV-2 test (adjusted OR = 1.32, 95% CI = 1.06 ~ 1.65, P < 0.05). A classifier to distinguish COVID-19 patients from the healthy controls based on the pharyngeal F. n was constructed and achieved an area under the curve (AUC) of 0.843 (95% CI = 0.688 ~ 0.940, P < 0.001). However, the level of fecal F. n and fecal F. p remained unaltered between groups. Besides, mNGS showed that the pharyngeal swabs of COVID-19 patients were dominated by opportunistic pathogens. Conclusions Pharyngeal but not fecal F. n was significantly increased in COVID-19 patients, clinicians should pay careful attention to potential coinfection. Pharyngeal F. n may serve as a promising candidate indicator for COVID-19.

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