Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

Mrochen, Daniel M.; Oliveira, Liliane Maria Fernandes de; Raafat, Dina; Holtfreter, Silva

doi:10.3390/ijms21197061

Cited by 23 publications

(18 citation statements)

References 240 publications

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“…Humanized mice with engrafted human immune cells may advance the translatability of mouse models of S. aureus infection ( Allen et al, 2019 ). Virulence of human-targeted toxins (such as PVL) is more likely to be revealed in mice with human hematopoietic cells ( Mrochen et al, 2020 ). Improved animal models may help determine which therapeutics should advance to clinical trials as antivirulence therapies continue to be explored.…”

Section: Discussionmentioning

confidence: 99%

Antivirulence Strategies for the Treatment of Staphylococcus aureus Infections: A Mini Review

2021

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Staphylococcus aureus is a Gram-positive bacterium capable of infecting nearly all host tissues, causing severe morbidity and mortality. Widespread antimicrobial resistance has emerged among S. aureus clinical isolates, which are now the most frequent causes of nosocomial infection among drug-resistant pathogens. S. aureus produces an array of virulence factors that enhance in vivo fitness by liberating nutrients from the host or evading host immune responses. Staphylococcal virulence factors have been identified as viable therapeutic targets for treatment, as they contribute to disease pathogenesis, tissue injury, and treatment failure. Antivirulence strategies, or treatments targeting virulence without direct toxicity to the inciting pathogen, show promise as an adjunctive therapy to traditional antimicrobials. This Mini Review examines recent research on S. aureus antivirulence strategies, with an emphasis on translational studies. While many different virulence factors have been investigated as therapeutic targets, this review focuses on strategies targeting three virulence categories: pore-forming toxins, immune evasion mechanisms, and the S. aureus quorum sensing system. These major areas of S. aureus antivirulence research demonstrate broad principles that may apply to other human pathogens. Finally, challenges of antivirulence research are outlined including the potential for resistance, the need to investigate multiple infection models, and the importance of studying antivirulence in conjunction with traditional antimicrobial treatments.

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Section: Discussionmentioning

confidence: 99%

Antivirulence Strategies for the Treatment of Staphylococcus aureus Infections: A Mini Review

2021

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“…CC130. CC1956) lacking human-specific virulence factors, such as superantigens and the IEC [Mrochen et al, 2018b[Mrochen et al, , 2020. Interestingly, laboratory mice also carry a large variety of S. aureus CCs, most of which likely originate from the human population but also lack Sa3int phages.…”

Section: Wild Rodents and Mice From Animal Facilitiesmentioning

confidence: 99%

The Role of hlb-Converting Bacteriophages in Staphylococcus aureus Host Adaption

Rohmer

Wolz

2021

Microb Physiol

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As an opportunistic pathogen of humans and animals, Staphylococcus aureus asymptomatically colonizes the nasal cavity but is also a leading cause of life-threatening acute and chronic infections. The evolution of S. aureus resulting from short- and long-term adaptation to diverse hosts is tightly associated with mobile genetic elements. S. aureus strains can carry up to four temperate phages, many of which possess accessory genes encoding staphylococcal virulence factors. More than 90% of human nasal isolates of S. aureus have been shown to carry Sa3int phages, whereas invasive S. aureus isolates tend to lose these phages. Sa3int phages integrate as prophages into the bacterial hlb gene, disrupting the expression of the sphingomyelinase Hlb, an important virulence factor under specific infection conditions. Virulence factors encoded by genes carried by Sa3int phages include staphylokinase, enterotoxins, chemotaxis-inhibitory protein, and staphylococcal complement inhibitor, all of which are highly human specific and probably essential for bacterial survival in the human host. The transmission of S. aureus from humans to animals is strongly correlated with the loss of Sa3int phages, whereas phages are regained once a strain is transmitted from animals to humans. Thus, both the insertion and excision of prophages may confer a fitness advantage to this bacterium. There is also growing evidence that Sa3int phages may perform “active lysogeny,” a process during which prophages are temporally excised from the chromosome without forming intact phage particles. The molecular mechanisms controlling the peculiar life cycle of Sa3int phages remain largely unclear. Nevertheless, their regulation is likely fine-tuned to ensure bacterial survival within different hosts.

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“…However, even though animal models remain necessary to decipher fundamental host-pathogen interactions and even though many potentially promising S. aureus anti-toxin therapeutics exist, most have failed in human trials or have not been tested. Therefore, the development of humanized mice with engrafted human immune cells for instance could help improve the translatability of animal investigations to human trials in the future [183][184][185]. This strategy will improve animal models, thus helping in deciding which treatments should proceed to clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus Toxins: An Update on Their Pathogenic Properties and Potential Treatments

Ahmad-Mansour

Loubet

Pouget

et al. 2021

Toxins

126

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Staphylococcus aureus is a clinically important pathogen that causes a wide range of human infections, from minor skin infections to severe tissue infection and sepsis. S. aureus has a high level of antibiotic resistance and is a common cause of infections in hospitals and the community. The rising prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA), combined with the important severity of S. aureus infections in general, has resulted in the frequent use of anti-staphylococcal antibiotics, leading to increasing resistance rates. Antibiotic-resistant S. aureus continues to be a major health concern, necessitating the development of novel therapeutic strategies. S. aureus uses a wide range of virulence factors, such as toxins, to develop an infection in the host. Recently, anti-virulence treatments that directly or indirectly neutralize S. aureus toxins have showed promise. In this review, we provide an update on toxin pathogenic characteristics, as well as anti-toxin therapeutical strategies.

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Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

Cited by 23 publications

References 240 publications

Antivirulence Strategies for the Treatment of Staphylococcus aureus Infections: A Mini Review

Antivirulence Strategies for the Treatment of Staphylococcus aureus Infections: A Mini Review

The Role of hlb-Converting Bacteriophages in <b><i>Staphylococcus aureus</i></b> Host Adaption

Staphylococcus aureus Toxins: An Update on Their Pathogenic Properties and Potential Treatments

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