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Microbes & Immunity Regulation of Staphylococcus aureus CP biosynthesis

synthesis by activating P SigA rather than P SigB and mediates sequential activation pattern supports the hypothesis that
the regulatory effects of ArlSR and Agr on capsule delayed capsule production is a strategic adaptation by S.
production. ArlRS promotes capsule gene expression aureus to optimize energy use: prioritizing the synthesis
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through MgrA-dependent pathways. The Agr quorum of colonization-related factors (e.g., adhesins and surface
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sensing system influences capsule production both by proteins) during early growth, while deferring energy-
activating cap gene expression through MgrA and by intensive virulence factors – such as capsules, secreted
inhibiting Rot. AI-2 quorum sensing molecules suppress proteases, toxins, and hemolysins – until later stages. This
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capsule production through the KdpDE two-component temporal regulation enables S. aureus to adapt efficiently
system, although its impact on P remains unclear. 77 to changing environmental conditions and host defenses.
SigB
CcpE, a positive regulator of the tricarboxylic acid cycle, Apart from genetic regulation, CP production is strongly
has shown contradictory effects on capsule production, influenced by environmental factors, including nutrient
likely due to variations in strain backgrounds or sampling availability and carbon dioxide (CO ) concentration.
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time points. CodY bind at two sites within P – Thakker et al. found that CP5-type S. aureus strain
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cap
upstream of P SigA and downstream of P SigB , extending into Reynolds produced robust capsules when cultured on solid
the coding region of the capA gene. Under nutrient-rich media, conferring resistance to neutrophil phagocytosis,
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conditions, CodY represses cap expression by preventing though this ability was lost in broth culture. Further
other positive regulators from binding. When nutrients quantitative testing showed that capsule production on
are limited, CodY affinity decreases, allowing factors like solid media was 100-fold higher than in the broth culture.
RbsR to bind and promote capsule production. This Further studies using a CP5 S. aureus strain isolated from
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mechanism partially explains the observed temporal a dairy cow mastitis sample evaluated capsule production
regulation: capsule synthesis is inhibited during early and across different media – brain–heart infusion (BHI),
mid-log phases but activated during late growth stages. Columbia, and mod 110 – each prepared in solid and liquid
Beyond transcriptional control, post-transcriptional forms, with or without the addition of lactose or glucose.
mechanisms also modulate CP biosynthesis. The CapAB The results showed that mod 110 medium produced the
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tyrosine kinase complex dynamically regulates enzymatic highest capsule yield, followed by Columbia, and BHI.
checkpoints through reversible phosphorylation, helping Across all media types, solid cultures presented higher
balance precursor allocation between CP synthesis and capsule production than liquid culture, and the addition
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competing pathways such as WTA and peptidoglycan of lactose increased the capsule yield of the CP5 strain.
biosynthesis. Moreover, the Ser/Thr kinase PknB, which Similar trends were observed for CP8 strains, where solid
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is activated by sensing lipid II levels, inhibits CapAB Columbia medium produced a higher capsule amount than
activity and the glycosyltransferase function of CapM, its liquid counterpart. In contrast, the addition of glucose
leading to decreased CP production. Such inhibition is promoted capsular production in a human-derived CP5 S.
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likely a protective strategy to preserve essential precursors aureus isolate. 88
for cell growth. In addition to the medium and nutrients, gas
Overall, the production of CPs in S. aureus is controlled compositions such as CO concentration also significantly
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by diverse regulatory factors and post-transcriptional affect CP synthesis. Under normal air conditions (0.03%
regulatory mechanisms. This complexity highlights the CO ), the capsule synthesis is inhibited. However, elevated
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tight control of capsule biosynthesis, underscoring its CO levels (1–5%) markedly increase capsule production.
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importance in the survival and pathogenicity of S. aureus. This phenomenon was evidenced in in vivo models,
including cystic fibrosis patients and rat granuloma pouch
5. Main factors affecting capsule models, where only 1 – 5% of S. aureus cells expressed
production CPs. However, when cultured aerobically in vitro, 70
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– 90% of these isolates re-expressed CPs. These data
Capsule production in S. aureus is temporally regulated
and varies throughout the bacterial growth cycle. During demonstrate that CO levels in host environments serve as
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a key environmental regulator of capsule production.
lag and logarithmic growth phases, cap gene expression
is inhibited, with significant upregulation occurring in Capsule production is enhanced by the addition of
the late logarithmic stage. This timing correlates with sodium chloride or under iron-deficient conditions. 65,90
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the activation of the key positive regulator SigB, which is In contrast, it is decreased when S. aureus is cultured in
itself inhibited by Rot and CodY in the earlier stages of the media containing yeast extract, under alkaline growth
growth. Studies have shown that SigB is often activated conditions, or in low-oxygen environments. 65,91,92 These
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and expressed in the late logarithmic phase. 80-85 This findings underscore the substantial impact of culture

Volume 2 Issue 4 (2025) 7 doi: 10.36922/mi.8392