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Microbes & Immunity Regulation of Staphylococcus aureus CP biosynthesis

capillary electrophoresis, and chromatography offer factors. Although the regulatory mechanisms
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higher sensitivity and resolution, they require specialized underlying cap gene expression remain incompletely
equipment and are not routinely used in all laboratories. understood, ongoing research continues to identify novel
Ultimately, the choice of quantification method should regulatory molecules. Most regulators modulate capsule
align with laboratory capabilities and experimental biosynthesis by directly or indirectly affecting P SigB
objectives. activity in the cap promoter region, while a few molecules
like SaeSR execute their regulatory roles through P
SigA
7. S. aureus without capsule suppression. Elucidating the CP regulatory network
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Capsule is the key virulence factor of many pathogenic is critical for understanding key pathogenic processes,
bacteria; encapsulated bacteria can use capsules to cause including bacterial colonization, infection dissemination,
invasive diseases. In contrast, acapsular bacteria show and persistence of S. aureus.
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hypersusceptible to C3 complement deposition and often The production of S. aureus capsules typically increases
present avirulence in animal models. Although CP5 during the late-log growth phase, though the molecular
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and CP8 are the predominant capsule types in human S. mechanisms governing this transition remain unclear.
aureus isolates, the majority of bovine mastitis-associated While constitutive SigB expression has been shown to
strains in Argentina lack capsule production. Grunert induce premature capsule production, strategies for
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22
et al. characterized two persistent S. aureus subtypes enhancing capsule yield require further investigation. This
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(HP/ST9 and LP/ST504) from dairy cattle and found knowledge gap highlights the need for comprehensive
that both strains exhibited phenotypic traits of lacking studies to clarify the temporal regulation of capsule
CP expression, low cytotoxicity, and high biofilm synthesis and its clinical implications.
production. During infection, host factors may drive
the emergence of regulatory phenotypes of S. aureus External factors, including growth medium
for better adaption to the infection site. Suligoy et al. composition, culture format (solid vs. liquid), CO levels,
2
revealed that S. aureus can switch CP expression on or off and nutrient availability, significantly influence S. aureus
34,87
in vivo, and stable non-encapsulated S. aureus mutants capsule synthesis. These stimuli likely exert their
can regain production of CP and staphyloxanthin for effects through bacterial signaling pathways or metabolic
bloodstream survival. 96 regulators, though the mechanistic interplay between
environmental cues and capsule production remains
The mechanisms of acapsular S. aureus formation are poorly characterized.
varied. Fischer et al. assessed CP and agr expression in
195 S. aureus strains from infected patients at a German Standardized methods for capsule isolation and
university hospital and found that loss of agr function quantification are critical for advancing research.
was frequently associated with an acapsular phenotype. Immunoassays such as ELISA with CP-type specific
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Inactivation of AgrC by IS256 insertion resulted in antibodies are the gold standard when validated reagents
stable acapsular phenotype in S. aureus strain HU-14. are available. When specific antibodies are unavailable,
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Similarly, deletions of sigB or rbsR significantly decreased alternative approaches like the phenol-sulfuric acid
CP expression in S. aureus isolates. MgrA is a strong method may be performed; however, standard protocols
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activator for capsule production, and a Becker mutant with would be beneficial for the research community.
the mgrA deletion presented an acapsular phenotype. In In conclusion, capsules play important roles in the
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addition, oxacillin treatment has been shown to suppress pathogenicity of S. aureus, and capsule production may
the expression of cap operon, resulting in an acapsular be driven by strain-specific traits, culture conditions,
phenotype. Collectively, these findings demonstrate that and growth phase dynamics. Further investigation of the
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an array of factors can affect CP expression in S. aureus molecular convergence between exogenous triggers and
isolates and their modulation may result in acapsular endogenous regulatory networks for S. aureus capsule
variants with altered pathogenic potential. production represents a vital research frontier with
implications for therapeutic development and infection
8. Conclusion and perspectives control strategies.

S. aureus capsule facilitates bacterial immune evasion Acknowledgments
through anti-phagocytic effects. The synthesis of
S. aureus CPs is mediated by enzymes encoded within the We thank Drs. Weilong Shang and Yi Yang from Army
cap gene cluster, 22,121 whose expression is tightly regulated Medical University for providing critical insights for the
during bacterial growth by over 10 identified regulatory manuscript.

Volume 2 Issue 4 (2025) 9 doi: 10.36922/mi.8392