ESKAPE Pathogens and Antimicrobial Resistance
ESKAPE Pathogens and Antimicrobial Resistance
The majority of nosocomial (hospital-acquired) infections are caused by a group of multi-drug resistant pathogenic bacteria known as ESKAPE Pathogens. A set of six extremely pathogenic bacteria known as ESKAPE is linked to serious nosocomial infections.
The acronym ESKAPE stands for
E= Enterococcus faecium
S= Staphylococcus aureus
K=Klebsiella pneumoniae
A= Acinetobacter baumannii
P= Pseudomonas aeruginosa
E= Enterobacter species
Since the early 2000s, microorganisms that are resistant to antibiotics have been considered a severe threat to human health. The severity and frequency of infections have increased due to the emergence of drug-resistant bacteria, necessitating an urgent focus on the creation of new potent antibiotics. In February 2017, the World Health Organization (WHO) produced a list of diseases for which new effective treatments were urgently needed. This list was intended to standardize the surveillance and research on these growing drug-resistant bacteria. A set of pathogenic bacteria with the designation “ESKAPE” and a “priority status” are included in this lengthy list.
The Infectious Disease Society of America (IDSA) recognized these bacteria as significant nosocomial infection causes in 2004 before the WHO did. However, only drug resistance was given considerable consideration, and the WHO issued a warning about the dangers of antimicrobial resistance before ESPAKE became a matter of concern.
The majority of the bacteria in this group are included in the 2019 Antimicrobial Resistant Threat List published by the CDC (Center for Disease Control and Prevention). The serious threat list includes Pseudomonas, Staphylococcus, and Enterococci, while the urgent threat list includes Acinetobacter and Enterobacterales (Klebsiella, Enterobacter).
List of ESKAPE Pathogens
The following six pathogenic bacteria are represented among the multi-drug resistance strains in ESKAPE
Enterococcus faecium
- It belongs to the genus Enterococcus, family Enterococcaceae, phylum Bacillota, and is a lactic acid fermenting, non-hemolytic, gram-positive cocci bacteria.
- It is located in the human gastrointestinal tract (GI tract) and is a component of the human microbiome. They do, however, now regularly cause infections in hospitalized patients due to their multi-drug resistance. They have the capacity to form biofilm and are thus engaged in illnesses linked to medical devices.
- Vancomycin-resistant E. faecium strains are the subject of particular attention (VR E. faecium).
- For example, ventilator-associated pneumonia and other respiratory tract infections (RTIs), catheter-associated urinary tract infections (UTIs), catheter-associated surgical wound infections, and bloodstream infections have all been linked to vancomycin-resistant strains of E. faecium.
Staphylococcus aureus
- S. aureus is a member of the genus Staphylococcus, family Staphylococcaceae, phylum Bacillota, and is a gram-positive, catalase-positive, facultatively anaerobic cocci bacteria.
- It makes up most of the skin and nasal cavity’s natural flora. However, it is frequently described as an opportunistic pathogen that causes RTIs, bacteremia, sepsis, UTIs, and food poisoning, among other illnesses.
- S. aureus is the most prevalent bacteria in everyone’s body and can form biofilms on medical equipment. They, therefore, represent the bulk of nosocomial infections globally. S. aureus is increasingly becoming a substantial hazard in hospital settings because of its resistance to the majority of existing therapies, leading to a rise in mortality in S. aureus infection cases.
- Nearly 50% of staphylococcal infections are caused by Methicillin-Resistant Staphylococcus aureus (MRSA), the most prevalent drug-resistant strain of S. aureus. MRSA is classified as a superbug and is usually linked to sepsis, UTIs, and skin and soft tissue infections.
Klebsiella pneumoniae
- A non-motile, oxidase-negative, gram-negative rod-shaped bacterium belonging to the Enterobacteriaceae family is K. pneumoniae.
- It is present in small amounts as part of the skin’s and GI tract’s natural flora in humans. It is one of the most frequent infections causing bacterial pneumonia while being commensal. It can also cause UTIs, surgical site infections, and catheter-associated infections, although it primarily causes pneumonia in patients on ventilators and in intensive care units.
- The pathogen on the list of immediate threats is K. pneumoniae which is carbapenem-resistant (CRKP).
Acinetobacter baumannii
- A. baumannii belongs to the genus Acinetobacter in the family Moraxellaceae of the phylum Pseudomonadota and is a species of aerobic, glucose-non-fermentative, Cocco-bacilli, Gram-negative Gammaproteobacteria.
- It typically exists in soil, water, and briefly in the flora of human skin. The number of nosocomial infections caused by A. baumannii is quickly rising, particularly RTIs, UTIs, and wound infections.
- Carbapenem-Resistant A. baumannii (CRAB), which is on the CDC and WHO’s urgent threat list, is one of the most hazardous strains of A. baumannii. In hospitalized patients, CRAB is primarily linked to ventilator-associated pneumonia (VAP), urinary tract infections (UTIs), and wound infections.
Pseudomonas aeruginosa
- P. aeruginosa belongs to the genus Pseudomonas, family Pseudomonadaceae, and phylum Pseudomonadota. It is a Gram-negative, rod-shaped, encapsulated, facultative anaerobic Gammaproteobacteria.
- An opportunistic nosocomial bacteria called P. aeruginosa can seriously affect the blood, the urinary system, the respiratory system, and wounds. It is the most frequent pathogen responsible for burn wounds and external ear infections.
- Globally, the number of P. aeruginosa strains that are multidrug-resistant is rising. Most of them have fought off treatment with conventional antibiotics. The mortality rate from an infection caused by such multiple-drug resistance bacteria can reach 60%. The CDC has added resistance to ciprofloxacin and levofloxacin to its list of significant threats.
Enterobacter species
- A genus of Gram-negative, lactose-fermenting, facultatively anaerobic, rod-shaped Gammaproteobacteria belonging to the Enterobacteriaceae family in the Pseudomonadota phylum is called Enterobacter.
- Numerous pathogenic species of Enterobacter, most of which infect immune-compromised people as opportunistic infections, are included. In the genus Enterobacter, common human infections include E. aerogenes, E. cloacae, and E. sakazakii.
- UTIs and RTIs are frequently linked to Enterobacter spp. Multidrug-resistant species are especially challenging to treat since they are resistant to the majority of -lactams and cephalosporins.
Clinical Characteristics of ESKAPE Pathogens
ESKAPE, which is responsible for roughly two thirds of all nosocomial infections worldwide, has the greatest impact on hospital-acquired illnesses. According to the US CDC, there are already 2 million nosocomial infections with 23,000 ESKAPE fatalities in the US alone, and the situation is expected to get worse yearly.
The following illnesses in hospitalized patients are caused by ESKAPE pathogens
- Pneumonia Acquired in a Hospital
- Infections of the Urinary Tract
- Diseases of the Skin and Wounds
- Infection at the surgical site
- Bacteremia and Soft Tissue Infections from Endocarditis
ESKAPE Pathogens Epidemiology
The majority of ESKAPE pathogen reports come from hospital settings. There is an upward tendency in their occurrence rate. As of 2021, there are no accurate statistics available due to a lack of an effective surveillance system, but findings from US CDCs and other European studies show that their frequency is rising quickly. Among the ESKAPE pathogens, S. aureus is the one that causes the most infections.
Antimicrobial Resistance in ESKAPE Pathogens
Pathogens from ESKAPE are multidrug-resistant (resistant to more than three classes of antibiotics). The majority of the antibiotics that were previously used to treat these bacteria are ineffective against them.
Pathogens associated with ESKAPE have evolved resistance to all or the majority of antibiotics from classes including -lactams, -Lactamase -inhibitors, macrolides, ciprofloxacin, tetracyclines, lipopeptides, quinolones and fluoroquinolones, and oxazolidinones, as well as the last line of defense like the majority of polymyxins, glycopeptides.
Enteroinvasive E. coli (EIEC)
Enteroinvasive E. coli (EIEC)
E. coli strains that are enteroinvasive (EIEC) are uncommon in both industrialized and developing nations. A period of watery diarrhea that occurs before the development of sparse dysenteric stools including blood and mucus is a characteristic of EIEC infections.
Pathogenic strains are mostly linked to a small number of limited O serotypes, specifically O124, O143, and O164. Shigella spp. and EIEC strains have close biochemical, genetic, and pathogenetic ties.
Disease Origin
It results in dysentery and intestinal ulceration (diarrhea with mucus and blood, called bacillary dysentery resembling Shigellosis).
Transmission Mode
Although person-to-person transmission does happen occasionally, EIEC outbreaks are typically water- or food-borne. Since EIEC has a larger infective dosage in volunteers than Shigella spp. does, the risk of person-to-person transmission is reduced.
E. coli enteroinvasive’s pathogenesis (EIEC)
The pathophysiology of EIEC includes
- Epithelial cell penetration
- Endocytic vacuole destruction
- Intracellular growth
- Cytoplasmic migration in a specific direction
- Extension into nearby epithelial cells
EIEC is invasive rather than toxic
A sequence of genes on a plasmid mediates bacterial invasion (pInv genes) into the colonic epithelium. The epithelial cell invasion is most crucially mediated by a plasmid-coded antigen called virulence marker antigen (VMA) (VMA).
- Following that, the bacteria lyse the phagocytic vacuole and begin to grow inside the cell.
- Actin tail development controls movement throughout the cytoplasm and into nearby epithelial cells (similar to that observed with Listeria).
- Colonic ulceration can result from this process of epithelial cell death and inflammatory infiltration.
Clinical traits
The bacteria can enter the colon and kill the epithelium, resulting in a condition that starts off with watery diarrhea. Only a small percentage of patients go on to develop the dysenteric form of the illness, which is characterized by fever, chills, malaise, cramps in the abdomen, and blood and leukocytes in stool samples.
Diagnosis
It can be challenging to diagnose EIEC strains apart from Shigella spp. and other E. coli strains, including non-pathogenic types. In general, proving that an organism is an EIEC requires showing that it has the biochemical profile of E. coli while also having the genotypic or phenotypic traits of Shigella spp.
HeLa cell invasion assay with ELISA for the detection of VMA
Serenity check (inoculation of bacterial suspension into guinea pig eyes produces conjunctivitis)
EIEC are biochemically unusual E. coli strains as compared to other E. coli strains because they are non-motile, lactose non-fermenters, and negative for lysine decarboxylase.
Opioids Recruit the Immune System to Cause Withdrawal Symptoms
Opioids Recruit the Immune System to Cause Withdrawal Symptom
According to a study, heroin causes T cells to breach the blood-brain barrier and wreak havoc on the brain, suggesting new strategies for preventing withdrawal.
Researchers have identified a previously unidentified immune system mechanism that leads to unstable and faulty connections among brain cells as one way that opioid use appears to cause withdrawal symptoms.
Despite the immune system’s long-standing association with opioid withdrawal, the new research, which was published January 19 in Cell, is the first to establish a connection between the immune system’s interactions with the brain’s blood-brain barrier and withdrawal, according to immunopathogenesis researcher Luis Montaner, a professor at the Wistar Institute in Philadelphia who was not involved in the study. The study, according to Montaner, provides researchers with “a roadmap for new clinical interventions to be tested” to prevent withdrawal and assist those recovering from opioid addiction or dependence wean off the drug safely while avoiding relapse. This is true even though some of the findings still need to be replicated and verified.
Toby Eisenstein, an immunologist and substance abuse researcher at Temple University who was not involved in the study, said that it “represents a major advance in the emerging field of neural-immune interactions and the role of immune cells and mediators in modulating neural processes during opioid exposure.” “The document is undoubtedly a huge step forward,” I firmly believe. Because opioids and the immune cells found in the new study have long been recognized to have immunosuppressive properties, Eisenstein says she was captivated by the paper’s assertion that withdrawal symptoms are related to an inflammatory immune response. Eisenstein talked about this in a 2019 review article on the effects of morphine on the immune system.
Moving on to a mouse model, the researchers discovered that administering heroin to mice increased the number of fragile-like Tregs and, consequently, the level of IFN- expression in the blood. IFN- was found to be more prominent in the nucleus accumbens, a part of the brain that regulates goal-directed behaviors and reward pathways, according to the analysis of samples taken from the heroin-treated mice. This finding has implications for understanding and treating addiction.
The heightened IFN- in that area, according to the study’s authors, suggests that the fragile-appearing Treg cells were successful in crossing the blood-brain barrier, the physical barrier that shields the brain from viruses (and many drugs) flowing via the body’s blood vessels. The study connected the vulnerability to breaches in the blood-brain barrier brought on by nucleus accumbens neurons’ production of C-C motif chemokine ligand 2 (Ccl2), which was aided by opioid exposure and enhances Treg trafficking into the brain. Eisenstein found that particularly intriguing: “The fact that the chemokine expression was coming from within the brain hints that brain cells have a larger role in the immune response than previously assumed.” Chemokines are responsible for trafficking immune cell subsets that express the receptor for the particular chemokine.
According to Eisenstein, “I believe the publication is significantly advancing the entire neuroimmune research and perhaps our understanding of what immune mediators and cells are doing in the brain.”
The researchers came to the conclusion that the mice developed withdrawal symptoms because the fragile-appearing Treg cells (and specifically the IFN- they released) were altering the nucleus accumbens and decreasing synaptic connections among neurons. However, staining showed that other cytokines and inflammatory agents remained at the same levels. In conclusion, the research shows that opioid stimulation “boosts the entry of fragile-like Tregs into the [central nervous system] and subsequently leads to structural and behavioral changes.”
Bacteria and Mental Health
Bacteria and Mental Health
Gastrointestinal flora can affect how you feel, think, or respond to stress. Researchers are currently looking into how these bacteria may impact mental health and mood.
Almost one in five American adults, children, and youth experience mental health issues annually or at some point in their lifetimes. There isn’t a single cause because various amounts of stress or underlying biological conditions can also contribute.
A list of stress-reduction methods, such as talking to a friend, practicing meditation, getting adequate sleep at night, or indulging in physical activity, may be suggested when the mood and mental health are at danger.
The possibility that stress and anxiety could start in the gut is less well-known. The relationship between the brain and gut is well known and frequently referred to as the “gut-brain axis,” with research showing that one’s emotions or mental state can affect their digestion or vice versa (see sidebar). It is now known that the “gut-brain axis” results from vagus nerve-mediated bidirectional communication between the brain and the nerve cells that line the gastrointestinal tract.
Gut-Brain-Microbiology Axis
A “microbiota-gut-brain axis” has emerged as a result of current research that has shifted its attention to the impact of bacteria on the stomach and brain. Dietary factors, such as the consumption of fermented foods and prebiotic-rich whole grains, fruits, and vegetables, have a significant impact on these bacteria, the species diversity of those microbes, and the populations of those microbes in our stomachs.
Short-chain fatty acids, precursors of neurotransmitters, and vitamins are examples of metabolites that gut microorganisms create and move through brain and circulatory pathways. Gut microorganisms are becoming more well recognized for their apparent impacts on the entire body, including the brain, and for affecting reactions to stress and anxiety based on these metabolites. Although still poorly understood, new observational and clinical investigations have given us a look into how intestinal neuronal cells in the gut may be directly influenced by gut microorganisms to affect mood and mental state.
Futures of Therapeutics, Mental Health, and Microbiota Dynamics
The body of knowledge about the ideal microbiome and the precise ways that changes and timing affect the brain continues to grow. The main objectives are to find methods for modifying the microbiota for the best possible brain growth and function throughout life.
Only observational research has provided us with the majority of our knowledge regarding gut microorganisms. The formation of the gut microbiota and baby and child brain development does, however, occur during certain periods that are becoming increasingly obvious.
Based on correlations between gut microbiota and cognitive outcomes, including fine motor abilities, social interactions, temperament, fear reaction, and stress management, these findings have been drawn. Another factor might be gender. For instance, only in boys do certain bacterial abundances correspond with extroversion, while only in girls do specific microbiome compositions link with fear reactivity.
Recent studies indicate that implementing tactics to direct microbiota growth or encourage its improvement may indirectly or directly impact brain structure and function for mental and emotional well-being. The following tactics may be used as part of these microbial shaping interventions
- Provision of prebiotics or certain nutrients for targeted alteration
- Whole microbial populations transplanted from a healthy donor
- Adding healthy bacteria through the use of probiotics
Early animal research has shown some encouraging findings. For instance, it has been discovered that animals with missing or changed gut microbiota exhibit blood-brain barrier dysfunction and behavioral deficiencies, which can be improved by reintroducing healthy microorganisms.