Tag: Staphylococcus aureus

Rising antibiotic resistance prompts shift to ecological research strategies in infection control

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In a recent article published in The Lancet Microbe, researchers discussed the need to enhance research on the interactions between bacterial pathogens and commensals within human microbiomes and host biology to develop innovative infection prevention and treatment strategies.

Study: Integrating research on bacterial pathogens and commensals to fight infections—an ecological perspective. Image Credit: TopMicrobialStock/Shutterstock.com

Background

The growing appreciation of the human microbiome’s role in health drives innovative disease prevention and treatment approaches.

This includes using microbiome signatures as biomarkers for diagnosing various diseases and exploring interventions like fecal microbiota transplantation.

Historically, research focused more on pathogens, but now, understanding the dynamic roles of pathogens and commensals is essential. Interdisciplinary collaboration offers new insights into the ecological factors driving bacterial behavior and the development of preventive and therapeutic strategies for infections.

This convergence of microbiome science and innovative approaches holds great potential for promoting human health.

Future research on commensal bacteria inspired by that on pathogens

Research on commensal bacteria is gaining momentum, inspired by the extensive study of major bacterial pathogens like Shigella flexneri, Staphylococcus aureus, and Streptococcus pneumoniae.

While pathogens have been extensively studied, commensals, particularly those from genera like Bacteroides, Clostridium, and Cutibacterium, have received less attention despite their potential clinical significance.

Evidence suggests that certain commensals play crucial roles in human health, producing compounds that inhibit pathogens and those that directly benefit the host. Understanding the host-specificity and biology of these beneficial commensals could offer insights into combating bacterial infections.

Additionally, exploring the mechanisms behind commensal-host interactions, such as adhesion to epithelial surfaces and modulation of mucosal immunity, could provide further avenues for research.

Expanding our understanding of fitness mechanisms of facultative human pathogens

Research on facultative human pathogens, which typically exist as commensals but can cause disease under certain conditions, is gaining importance, considering the global rise in antimicrobial resistance.

While much attention has been given to understanding the virulence mechanisms of major pathogens like S. aureus and S. pneumoniae, the factors influencing the fitness of these organisms during their commensal phase have been largely overlooked.

This oversight is particularly concerning given the increasing prevalence of antibiotic-resistant pathogens, including those grouped as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp).

Understanding why certain antibiotic-resistant clones spread more effectively than others is crucial for developing effective control strategies.

Applying ecological concepts to studying pathogenic bacteria could shed light on their success in competing with other microbiome members. Factors such as nutrient utilization, resistance to antimicrobial molecules, and adhesion to host epithelial surfaces play important roles in determining a bacterial species’ long-term success within a host and its ability to spread to new hosts.

Investigating the mechanisms underlying vertical and lateral transmission of bacteria is also crucial, as it can provide insights into the dynamics of microbiome colonization and infection spread.

The severity and type of infection caused by pathogens can influence their spread among hosts. For example, pathogens like S. flexneri, causing diarrheal diseases, may spread through contaminated sewage, while those like S. aureus, causing skin infections, may spread through direct contact between individuals.

Accidental pathogens, which typically lack aggressive toxins but possess immune-evasion mechanisms, may persist in human microbiomes more readily than professional pathogens.

However, professional pathogens can also cause opportunistic infections, particularly in immunocompromised individuals.

Integrative understanding of fitness of bacterial commensals and pathogens can help with infection prevention

Understanding commensal and pathogenic bacteria within their natural habitats can provide valuable insights for controlling infections and addressing microbiome-related disorders.

Commensal bacteria exhibit complex effects on infectious diseases, employing various defense strategies such as antimicrobial production and metabolic interference to inhibit pathogen colonization.

Microbiome restoration through fecal microbiota transplantation has shown promise in treating infections, but standardized approaches are needed. Utilizing defined commensal communities for microbiome editing could offer more consistent results and personalized treatment options.

However, antibiotic treatment, primarily with broad-spectrum antibiotics, can disrupt the microbiome and fuel antibiotic resistance.

Commensals play a crucial role in resistance gene transfer to pathogens, highlighting the need to monitor key commensal species alongside major pathogens.

Ecological approaches to infection research can help identify vulnerabilities in pathogens, leading to the development of targeted anti-fitness drugs and anti-virulence compounds. Understanding the interplay between pathogens and mucosal immunity is essential for developing mucosal vaccines against potentially pathogenic microbiome members.

Conclusion

In conclusion, understanding the interaction between commensal and pathogenic bacteria within their ecological contexts offers promising avenues for infection prevention and treatment.

By leveraging the protective mechanisms of commensals and targeting pathogen virulence, tailored interventions can enhance host defenses and suppress pathogen proliferation.

Moreover, the development of mucosal vaccines and microbiome-based therapies offers new strategies for infection control. Integrating ecological principles into infection research provides a holistic framework for combating infectious diseases and addressing antimicrobial resistance, ultimately optimizing human health.

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April 12, 2024
How microbes influence healing and infection risks
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In a recent Nature Reviews Microbiology study, researchers review how the wound microbiota interferes with skin repair processes and facilitates infection onset by modulating host immune responses.

Study: The wound microbiota: microbial mechanisms of impaired wound healing and infection. Image Credit: A3pfamily / Shutterstock.com

Background

The skin protects the human body from the potentially harmful effects of invading pathogens and chemicals. Any injury or damage to the skin can lead to wound development; therefore, dressing and infection control are standard practices of wound care.

The wound-healing process involves coagulation, hemostasis, inflammation, cell proliferation and migration, and tissue remodeling. Any alteration to these processes can lead to delayed wound healing and the development of a chronic wound.

Non-healing and chronic wounds are associated with certain risk factors, including advanced age and the presence of specific comorbidities, such as diabetes, obesity, systemic diseases, immunosuppressive diseases, and autoimmune diseases.

Microorganisms colonizing in wounds, collectively referred to as the wound microbiota, can significantly impact the healing process. While some microorganisms facilitate faster skin repair, some can acquire virulence factors and antibiotic resistance, thereby increasing the risk of infection.

Both exogenous and endogenous microorganisms can contaminate an open wound. The wound can facilitate microbial growth by exposing subcutaneous tissues and nutrients, which can subsequently lead to the colonization of microorganisms in the wound. This type of colonization can cause local infection and biofilm formation, which has the potential to spread to other tissues and organs.

Wound microbiota composition

The most common microbial populations found in both acute and chronic wounds include Staphylococcus spp., Pseudomonas spp., Corynebacterium spp., Enterococcus spp., Streptococcus spp. and Cutibacterium spp, all of which are microorganisms that are also commonly found in healthy skin microbiota.

Staphylococcus aureus

A skin wound can significantly alter its surrounding environment through the secretion of molecules from damaged tissues to support the growth, invasion, adhesion, and migration of pathogens such as Staphylococcus aureus. High abundance of fibronectin- and collagen-binding proteins facilitates Staphylococcus aureus to easily invade broken skin and induce intracellular infection.

Staphylococcus aureus also produces pore-forming toxins that disrupt the host cell membrane to prevent immune clearance. Furthermore, serine proteases produced by this bacterium act as enterotoxins that induce chronic inflammation and create severe, non-healing diabetic wounds.

Staphylococcus aureus has multiple master regulators, including the accessory gene regulator quorum-sensing system and sarA, which help activate its virulence factors. Glucose transporters acquired by Staphylococcus aureus further induce the production of virulence factors under hyperglycemic conditions.

Pseudomonas aeruginosa

Pseudomonas aeruginosa is a pathogen that can be found in burn wounds, chronic surgical wounds, and diabetic wounds. High-level antibiotic resistance and robust ability to form biofilm allow Pseudomonas aeruginosa to create chronic and non-healing wounds. Pseudomonas aeruginosa also comprises a type III secretion system that controls the production of effector toxins, further facilitating the production of virulence factors.

Streptococcus

Streptococcus spp., including β-Hemolytic group A streptococci (GAS), group B streptococci (GBS), and group C streptococci, can be found in invasive and non-invasive wounds.

GAS bacteria contain multiple adhesins that promote their access to diverse tissue surfaces. Virulence factors present in GAS bacteria work in synergy to bind to and activate host plasminogens and create a proteolytic environment that alters wound-site architecture.

Anaerobic bacteria

Anaerobic bacteria commonly found in wound infections include Finegoldia magna, B. fragilis, and Clostridium perfringens. These bacteria can be introduced to the wound during injury, such as bite or abdominal penetrating wounds. In diabetic or other chronic wounds, these bacteria thrive in conditions of low tissue oxygenation and can exist in mixed facultative and obligate anaerobes communities.

Fungi

Candida albicans is a fungal species most commonly found in chronic, surgical, and burn wounds. These fungi can enter host cells by binding to E-cadherin and triggering endocytosis. The pathogenicity of C. albicans is dependent on its ability to switch between yeast and a highly invasive hyphal phenotype.

Viruses

Viruses can also impact wound healing and skin repair processes. Whereas specific bacteriophages can worsen wound infections by increasing the virulence of bacteria they have infected, other bacteriophages can improve wound healing by changing bacterial virulence.

Risk factors for wound infection

The outcomes of wound microbial infections primarily depend on microbial virulence, polymicrobial interactions, and complex crosstalk between microbes and the wound microenvironment.

Multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) or multidrug-resistant Pseudomonas aeruginosa, can complicate the treatment of wound infections. Likewise, a compromised immune system or certain genetic factors can further delay the wound-healing process and increase the risk of infection.

Microbial virulence is also an important determinant of wound outcomes and treatment modalities. Wound bioburden, characterized by microbial load, microbial diversity, and the presence of pathogenic microbes, is a key contributor to delayed wound healing and infection onset.
Journal reference:

Uberoi, A., McCready-Vangi, A., & Grice, E. A. (2024). The wound microbiota: microbial mechanisms of impaired wound healing and infection. Nature Reviews Microbiology. doi:10.1038/s41579-024-01035-z.
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April 8, 2024
Croatian sea fennel may contain a treasure trove of preservative and anti-aging metabolites
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In a recent study published in the journal Foods, researchers evaluated the biological activity of hydrolats and essential oils derived from French and Croatian sea fennel. Despite being the main by-product obtained from the isolation of essential oils from these plants, research into the biochemical properties of fennel-derived volatiles remains lacking. Combinations of hydrodistillation, chemical analysis, and biological activity analysis revealed that the chemistry of the two sea fennel populations under study differed significantly in both composition and biological function. The Croatian sea fennel particularly displays beneficial anti-collagenase and anti-tyrosinase activity, highlighting its anti-aging potential and cosmetic application.

Study: Volatiles from French and Croatian Sea Fennel Ecotypes: Chemical Profiles and the Antioxidant, Antimicrobial and Antiageing Activity of Essential Oils and Hydrolates. Image Credit: Happy window / Shutterstock

What is sea fennel?

Sea fennel is a common name that refers to a group of perennial aromatic herbs belonging to the carrot (Apiaceae) family. They can be found growing on beaches, rocks, breakwaters, and piers around the world. Sea fennels are halophytic plants rich in nutritional and organoleptic compounds. Given the increasing global consumer demand for the use of safe and natural ingredients in cosmetics, pharmaceuticals, and other essential oil (EO)-using products, research has extensively explored the biological applications of fennel-derived EOs.

Unfortunately, the potential benefits of volatiles obtained during the isolation of EOs from the fennel plant remain unstudied. Often termed ‘hydrolats,’ research conducted on these volatiles from other herb sources reveals that they present numerous benefits over EOs, including potent bioactive functions and reduced dosage-dependent cytotoxicity. Additionally, despite being traditionally used in perfume and cosmetic manufacture, sea fennels remain understudies for their clinical and nutraceutical potential. Limited information on EO compositions from different regions suggests that they may not all be the same, with concentrations of metabolites, especially dillapiole.

Understanding the geographical variability in sea fennel biochemical profiles and the potential of both their EOs and volatiles in biological, cosmetic, and pharmaceutical industries would allow for the sustainable and eco-friendly use of safe and naturally derived products, often considered waste (hydrolats). These findings may further guide future research on these abundant and near-ubiquitous yet poorly understood plants.

About the study

In the present study, researchers used a combination of chemical and biological analyses to investigate the biochemical composition and biological properties of sea fennel derived from French and Croatian regions. The study samples comprised 2 kg of sea fennel aerial parts collected from Dalmatia (Mediterranean ecotype) and the Brittany shoreline (Atlantic ecotype) in October 2022. Hydrodistillation was used for EO extraction, with extracted EOs dried using sodium sulfate (Na₂SO₄).

Volatiles from hydrolats were extracted using headspace solid-phase microextraction (HS-SPME), following which gas chromatography-mass spectrometry (GC-MS) was used for chemical composition analysis. The antioxidant activity of EOs and volatiles was estimated using a microplate spectrometric reader. Reduction ability was tested using a Ferric Reducing Antioxidant Power (FRAP) assay. Biological assays further included the synthetic stable 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), the nitric oxide radical (NO), and the hydroperoxyl radical (HOO) assays.

The antimicrobial activities of fennel-derived samples were computed using Staphylococcus aureus ATCC 33862 (gram-positive) Escherichia coli ATCC 1053, and Pseudomonas aeruginosa ATCC 27853 (gram-negative) bacterial strains. Mushroom tyrosinase with L-tyrosine as substrate was used to evaluate anti-tyrosinase activity, elastase from porcine pancreas Type IV E0258 with N-Succinyl-Ala-Ala-Ala-p-nitroanilide (SANA) as substrate evaluated anti-elastase activity, and the Enzo Life Sciences MMP-1 kit for anti-collagenase activity. The Tukey post hoc test was used for statistical comparisons between cohorts.

Study findings

French sea fennel EO extracts were found to be slightly more chemically diverse than their Croatian counterparts, having 13 components in place of the latter’s 12. Dillapiole, carvacryl methyl ether, and γ-terpinene were found to be the main bioactive components of French sea fennel EOs, while Croatian sea fennel EOs were found rich in sabinene and limonene, highlighting that these populations are unique chemotypes.

“It is hard to draw general conclusions about the causes of the differences in the chemical composition of sea fennel EOs, as they may be due to the different abiotic and biotic factors that affect the synthesis and accumulation of plant secondary metabolites, such as the harvest location or geographical variations, plant vegetation/harvest period/growth cycle, plant part used, climatological factors, soil abiotic factors, etc. However, our results agreed with the conclusions of other authors, according to which the main reason is simply the existence of different plant chemotypes (intraspecific variability).”

The complexity of French sea fennel extends to their volatiles, with these plants containing 32 identifiable compounds to Croatian sea fennel’s 17. Dillapiole, thymol methyl ether, and γ-terpinene were found in the highest concentration in French sea fennel volatiles, while the Croatian samples were observed to contain terpinene-4-ol and 10-(acetyl methyl)-3-care.

Antioxidant tests revealed that sea fennel-derived compounds’ antioxidant potential pales compared to gallic acid, the gold standard in natural phenolic antioxidants. FRAP test values were found to vary between 0.77 and 1.34 µM Fe2+/L, with similar observations made in DPPH assays. Reducing potential analyses paint a different picture, with both French and Croatian sea fennels displaying reducing potential, slightly higher in the latter. Surprisingly, the potency of volatiles and hydrolats was found to be more than three-fold higher than a corresponding amount of EO, highlighting their future industrial potential.

The observable advantages of volatiles over EOs were also observed in the radical scavenging efficiencies of the two cohorts, with volatiles being 3.8 times more efficient than their EO counterparts.

“French EO showed no antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa, but a slight activity against Staphylococcus aureus (8 mm). Conversely, the Croatian EO moderately inhibited the growth of P. aeruginosa (8 mm), but strongly inhibited that of the other two bacterial strains (18 and 25 mm for E. coli and S. aureus, respectively). Interestingly, the CRO EO’s inhibition of the latter bacterial strain was as strong as that of the commonly used bactericidal streptomycin. Furthermore, neither the French nor the Croatian hydrolates showed any antimicrobial effect.”

Importantly, Croatian sea fennel was observed to display anti-tyrosinase and anti-collagenase activity, both of which were absent in French sea fennel. This highlights Croatian sea fennel as the target of future bioprospecting studies to discover safe and natural anti-aging cosmetic additives.
Journal reference:

Politeo, O., Ćurlin, P., Brzović, P., Auzende, K., Magné, C., & Generalić Mekinić, I. (2023). Volatiles from French and Croatian Sea Fennel Ecotypes: Chemical Profiles and the Antioxidant, Antimicrobial and Antiageing Activity of Essential Oils and Hydrolates. Foods, 13(5), 695, DOI – 10.3390/foods13050695, https://www.mdpi.com/2304-8158/13/5/695
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February 27, 2024
Researchers uncover how deadly MRSA pneumonia inhibits body’s antimicrobial activity

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In a recent study published in the American Journal of Physiology-Lung Cellular and Molecular Physiology, a group of researchers examined how heparan sulfate (HS)shedding impacts cathelicidin efficacy in Methicillin-Resistant Staphylococcus aureus (MRSA) pneumonia.

Study: Bacterial pneumonia-induced shedding of epithelial heparan sulfate inhibits the bactericidal activity of cathelicidin in a murine model. Image Credit: Tatiana Shepeleva/Shutterstock.com

Background

Pneumonia, particularly caused by MRSA, is a leading cause of infectious mortality. The mechanisms leading to Staphylococcal pneumonia are not fully understood. This study explores the interactions between MRSA, the pulmonary epithelial glycocalyx, and antimicrobial peptides (AMPs) in pneumonia.

The focus is on the HS enriched glycocalyx, a sulfated layer lining the alveoli known to bind cationic proteins. We examine the shedding of HS into the airspace following lung injury and its potential impact on lung function and interactions with AMPs. Specifically, we investigate how shed HS oligosaccharides, especially during bacterial pneumonia, interact with AMPs like cathelicidins, impacting the host immune response and pathogen dynamics.

Further research is needed to fully understand the mechanisms by which HS shedding impacts AMP function, offering potential for novel therapeutic strategies in pneumonia treatment.

About the study

In this study, following the University of Colorado’s Institutional Animal Care and Use Committee (IACUC) and Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines, male C57BL6 mice underwent intratracheal MRSA instillation, followed by bronchoalveolar lavage (BAL) for fluid analysis. Researchers used mass spectrometry to measure HS in BAL fluid, blind to treatment groups for objective results.

Additionally, the team innovatively collected airspace fluid from pneumonia patients using heat and moisture exchanger (HME) filters at Vanderbilt University Medical Center under an approved Institutional Review Board (IRB) protocol. This aimed to detect lung changes due to respiratory failure.

The study employed surface plasmon resonance (SPR) to examine the binding kinetics between AMP and HS, providing real-time, label-free interaction insights. Concurrently, bacterial growth curves were studied under various conditions to assess the effect of different heparin types on MRSA strains.

Detailed processes of bacterial ribonucleic acid (RNA) isolation and sequencing were conducted, involving MRSA culture in heparin or saline, followed by RNA extraction and sequencing. These steps were crucial in exploring transcriptomic changes and enhancing understanding of bacterial pneumonia dynamics.

The research also included minimum inhibitory concentration (MIC) quantification for different pneumonia pathogens against AMP in varying HS concentrations. This was key in evaluating how HS influences AMP effectiveness against bacterial infections. Rigorous statistical analysis ensured the study’s findings were reliable and valid.

Study results

In the present study, researchers utilized a murine model of MRSA pneumonia. Mass spectrometry analyses revealed a significant increase in HS in the airspace lining fluid of MRSA-infected mice compared to saline controls. Notably, this increase was characterized by a higher abundance of sulfated HS, particularly multi-sulfated disaccharides. Complementary analyses with HME filter samples indicated higher HS levels in patients with gram-negative pneumonia compared to those with gram-positive pneumonia, suggesting a nuanced relationship between bacterial etiology and HS shedding.

Despite the observed increase in shed HS in the lung environment, the study found no direct impact of HS on MRSA growth or gene transcription. Experiments involving various sizes and sulfation patterns of HS showed no significant changes in MRSA growth or transcriptomic response. This finding suggested that HS, while a significant component of the lung milieu post-injury, did not directly inhibit bacterial growth or induce changes in bacterial gene expression.

The study further delved into the interactions between HS and host immune mediators. Using surface plasmon resonance (SPR), the researchers quantified the binding of HS with murine cathelicidin-related antimicrobial peptide (mCRAMP). The strong binding observed indicated a likely interaction in vivo, which could potentially influence the host response to bacterial infection.

Most critically, the study investigated the functional implications of HS binding to mCRAMP. Focusing on common nosocomial pneumonia pathogens including MRSA, Klebsiella pneumoniae, and Pseudomonas aeruginosa, the research employed a modified radial diffusion assay to assess the MIC of mCRAMP against these bacteria.

Results showed significant increases in MIC with higher HS concentrations, indicating a diminished bactericidal effect of mCRAMP in the presence of HS. This finding was particularly noteworthy as it highlighted the complex interplay between HS and host defense mechanisms, where HS, despite not directly affecting MRSA growth, significantly altered the efficacy of an antimicrobial peptide.

Conclusion

Overall, the study underscored the intricate dynamics within the pulmonary environment following bacterial pneumonia. The acute shedding of epithelial HS, particularly when enriched in sulfated forms, presented a nuanced challenge to the host’s immune response, potentially influencing the effectiveness of innate immune mechanisms against bacterial pathogens.

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February 7, 2024