The iron-regulatory hormone hepcidin is induced early in infection, causing iron sequestration in macrophages and decreased plasma iron; this is proposed to limit the replication of extracellular ...microbes, but could also promote infection with macrophage-tropic pathogens. The mechanisms by which hepcidin and hypoferremia modulate host defense, and the spectrum of microbes affected, are poorly understood. Using mouse models, we show that hepcidin was selectively protective against siderophilic extracellular pathogens (Yersinia enterocolitica O9) by controlling non–transferrin-bound iron (NTBI) rather than iron-transferrin concentration. NTBI promoted the rapid growth of siderophilic but not nonsiderophilic bacteria in mice with either genetic or iatrogenic iron overload and in human plasma. Hepcidin or iron loading did not affect other key components of innate immunity, did not indiscriminately promote intracellular infections (Mycobacterium tuberculosis), and had no effect on extracellular nonsiderophilic Y enterocolitica O8 or Staphylococcus aureus. Hepcidin analogs may be useful for treatment of siderophilic infections.
•In mouse models, hepcidin participates in innate immunity by controlling NTBI.•NTBI-dependent infections can be treated with hepcidin agonists in mouse models of hereditary hemochromatosis or parenteral iron overload.
Staphylococcus aureus – a commensal of the human skin, nares and gastrointestinal tract – is also a leading cause of bacterial skin and soft tissue infection (SSTIs), bacteremia, sepsis, peritonitis, ...pneumonia and endocarditis. Antibiotic-resistant strains, designated MRSA (methicillin-resistant S. aureus), are common and represent a therapeutic challenge. Current research and development efforts seek to address the challenge of MRSA infections through vaccines and immune therapeutics. Mice have been used as experimental models for S. aureus SSTI, bacteremia, sepsis, peritonitis and endocarditis. This work led to the identification of key virulence factors, candidate vaccine antigens or immune-therapeutics that still require human clinical testing to establish efficacy. Past failures of human clinical trials raised skepticism whether the mouse is an appropriate model for S. aureus disease in humans. S. aureus causes chronic-persistent infections that, even with antibiotic or surgical intervention, reoccur in humans and in mice. Determinants of S. aureus evasion from human innate and adaptive immune responses have been identified, however only some of these are relevant in mice. Future research must integrate these insights and refine the experimental mouse models for specific S. aureus diseases to accurately predict the failure or success for candidate vaccines and immune-therapeutics.
•Staphylococcus aureus is a human commensal•S. aureus causes invasive and recurrent diseases•S. aureus infections fail to elicit protective immune responses•S. aureus disease attributes can be studied in experimental mouse models of infection
In this report, implementation of a MRSA bundle (nasal surveillance for MRSA, contact precautions for patients with MRSA, hand hygiene, and an institutional culture change whereby infection control ...was everyone's responsibility) was associated with a significant decline in MRSA transmission.
Methicillin-resistant
Staphylococcus aureus
(MRSA) infections are a problem in the United States
1
and elsewhere. MRSA is one of the most common causes of ventilator-associated pneumonia, bloodstream infection associated with central venous catheters, and surgical-site infections.
1
,
2
In 2001, the Veterans Affairs (VA) Pittsburgh Healthcare System began working with the Pittsburgh Regional Healthcare Initiative and the Centers for Disease Control and Prevention (CDC) to eliminate health care–associated MRSA infections with the use of a “MRSA bundle.” The bundle, which was based on published guidelines, comprised universal nasal surveillance for MRSA colonization, contact precautions for patients who were carriers of MRSA, hand . . .
Staphylococci are important opportunistic pathogens in most animal species. Among the most relevant species are the coagulase positive species
Staphylococcus aureus and
Staphylococcus ...pseudintermedius. Methicillin resistance has emerged as an important problem in both of these organisms, with significant concerns about animal and public health. The relative importance of these staphylococci on different animal species varies, as do the concerns about zoonotic transmission, yet it is clear that both present a challenge to veterinary medicine.
Staphylococcus aureus causes many types of human infections and syndromes—most notably skin and soft tissue infections. Abscesses are a frequent manifestation of S. aureus skin and soft tissue ...infections and are formed, in part, to contain the nidus of infection. Polymorphonuclear leukocytes (neutrophils) are the primary cellular host defense against S. aureus infections and a major component of S. aureus abscesses. These host cells contain and produce many antimicrobial agents that are effective at killing bacteria, but can also cause non-specific damage to host tissues and contribute to the formation of abscesses. By comparison, S. aureus produces several molecules that also contribute to the formation of abscesses. Such molecules include those that recruit neutrophils, cause host cell lysis, and are involved in the formation of the fibrin capsule surrounding the abscess. Herein, we review our current knowledge of the mechanisms and processes underlying the formation of S. aureus abscesses, including the involvement of polymorphonuclear leukocytes, and provide a brief overview of therapeutic approaches.
Staphylococcus aureus (S. aureus) is a notorious pathogen and one of the most frequent causes of biofilm-related infections. The treatment of S. aureus biofilms is hampered by the ability of the ...biofilm structure to shield bacteria from antibiotics as well as the host’s immune system. Therefore, new preventive and/or therapeutic interventions, including the use of antibody-based approaches, are urgently required. In this review, we describe the mechanisms by which anti-S. aureus antibodies can help in combating biofilms, including an up-to-date overview of monoclonal antibodies currently in clinical trials. Moreover, we highlight ongoing efforts in passive vaccination against S. aureus biofilm infections, with special emphasis on promising targets, and finally indicate the direction into which future research could be heading.
S. aureus and other staphylococci are the most common causes of persistent biofilm-associated infections, which are inherently resistant to antibiotics as well as the host’s immune system.
Antibody-based approaches can be used to combat biofilms. Antibodies can prevent bacterial attachment and/or biofilm maturation, or even disperse mature biofilms, as shown in in vitro and preclinical studies.
Several sophisticated techniques can be used for the generation of human monoclonal antibodies, to be ultimately employed in research or clinical settings.
Since antibodies against surface structures proved unsuccessful in clinical trials so far, current research is focussed on S. aureus toxins, and biofilm matrix components.
Multivalent vaccines, with a special emphasis on biofilm-related targets, are the strategy of choice for active as well as passive vaccination.
Staphylococcus aureus is both a commensal organism and also an important opportunistic human pathogen, causing a variety of community and hospital-associated pathologies, such as bacteremia-sepsis, ...endocarditis, pneumonia, osteomyelitis, arthritis and skin diseases. The resurgence of S. aureus during the last decade in many settings has been facilitated not only by bacterial antibiotic resistance mechanisms but also by the emergence of new S. aureus clonal types with increased expression of virulence factors and the capacity to neutralize the host immune response. Prevention of the spread of S. aureus infection relies on the use of contact precautions and adequate procedures for infection control that so far have not been fully effective. Prevention using a prophylactic vaccine would complement these processes, having the potential to bring additional, significant progress toward decreasing invasive disease due to S. aureus.
Staphylococcus aureus , both methicillin susceptible and resistant, are now major community-based pathogens worldwide. The basis for this is multifactorial and includes the emergence of epidemic ...clones with enhanced virulence, antibiotic resistance, colonization potential, or transmissibility. Household reservoirs of these unique strains are crucial to their success as community-based pathogens. Staphylococci become resident in households, either as colonizers or environmental contaminants, increasing the risk for recurrent infections. Interactions of household members with others in different households or at community sites, including schools and daycare facilities, have a critical role in the ability of these strains to become endemic. Colonization density at these sites appears to have an important role in facilitating transmission. The integration of research tools, including whole-genome sequencing (WGS), mathematical modeling, and social network analysis, has provided additional insight into the transmission dynamics of these strains. Thus far, interventions designed to reduce recurrent infections among household members have had limited success, likely due to the multiplicity of potential sources for recolonization. The development of better strategies to reduce the number of household-based infections will depend on greater insight into the different factors that contribute to the success of these uniquely successful epidemic clones of S. aureus.
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