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Acidic pH Modulates Cell Wall and Melanization in Paracoccidioides brasiliensis, Affecting Macrophage Interaction

Summary

A dangerous fungal infection called paracoccidioidomycosis affects people in Latin America. Researchers found that when this fungus encounters acidic conditions similar to those inside immune cells in the body, it protects itself by producing a dark pigment called melanin and changing its cell surface. These changes help the fungus hide from the immune system and reduce the ability of immune cells called macrophages to attack and destroy it.

Background

Paracoccidioides brasiliensis is a thermally dimorphic fungal pathogen causing paracoccidioidomycosis (PCM), a neglected systemic mycosis endemic in Latin America. The fungus’s virulence is closely associated with its capacity to survive under hostile host conditions, including acidic environments found in phagolysosomes, inflamed tissues, and granulomatous lesions.

Objective

This study aimed to investigate how P. brasiliensis responds to acidic pH conditions and determine whether acidic pH induces melanization, modulates cell wall composition, and alters the interaction with macrophages.

Results

Acidic pH reduced fungal growth while maintaining viability above 90% and triggered increased melanin production with enhanced laccase activity and upregulation of DHN-melanin biosynthetic pathway genes. Cell wall remodeling included increased surface chitin and reduced mannan content, with decreased stability to Congo Red. P. brasiliensis grown at acidic pH exhibited reduced phagocytosis by macrophages and attenuated pro-inflammatory responses including TNF-α and nitric oxide production.

Conclusion

Environmental acidification promotes P. brasiliensis adaptations including melanization and cell wall remodeling that enhance survival and modulate host-pathogen interactions, contributing to fungal virulence. These findings provide insights into the pathobiology of PCM and mechanisms of fungal immune evasion that may inform therapeutic strategies.
  • Published in:Journal of Fungi (Basel),
  • Study Type:Experimental In Vitro Study,
  • Source: PMID: 40985403, DOI: 10.3390/jof11070504
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