# Host Serum Amyloid A1 Facilitates Streptococcus pneumoniae Adaptation to Acidic Stress Induced by Pneumococcal Anaerobic Metabolism

## TL;DR

This study shows that the host protein SAA1 helps Streptococcus pneumoniae survive acidic conditions during infection.

## Contribution

The study reveals a new mechanism where S. pneumoniae uses host SAA1 to adapt to acid stress during infection.

## Key findings

- SAA1 levels in bronchoalveolar lavage fluid decreased after S. pneumoniae infection.
- Serum and recombinant SAA1 increased S. pneumoniae resistance to acidic byproducts like formic acid.
- Fluorescence microscopy confirmed SAA1 internalization by S. pneumoniae.

## Abstract

Streptococcus pneumoniae (S. pneumoniae) is a leading cause of pneumonia, and its interaction with host acute-phase proteins remains underexplored. Serum amyloid A1 (SAA1), an acute-phase protein, plays a crucial role in immune modulation. This study investigates the role of SAA1 in the early stages of respiratory infection by S. pneumoniae and its potential contribution to bacterial adaptation under acidic stress. We used a murine nasal infection model to simulate the early phase of S. pneumoniae invasion into the lower respiratory tract. Levels of SAA1 and C-reactive protein (CRP) in bronchoalveolar lavage fluid (BALF) and serum were quantified using ELISA. In vitro assays examined the effect of serum and recombinant SAA1 on bacterial survival under acidic conditions. Fluorescence-labeled recombinant SAA1 and microscopy were utilized to assess SAA1 internalized by S. pneumoniae. Following nasal infection, SAA1 levels in BALF were significantly reduced, whereas CRP levels remained unchanged. In vitro, serum enhanced S. pneumoniae’s resistance to acidic byproducts including formic, lactic, and acetic acids. Specifically, formic acid promoted bacterial uptake of SAA1, and this internalization improved bacterial tolerance to acidic conditions. Fluorescence microscopy confirmed that SAA1 is internalized by S. pneumoniae. S. pneumoniae can internalize SAA1 to bolster resistance to acid stress, particularly formic acid. This study reveals a novel host–pathogen interaction mechanism wherein S. pneumoniae exploits host acute-phase proteins for environmental adaptation, offering new insights into bacterial survival strategies during infection.