No abstract

We found that the autophagic machinery could effectively eliminate pathogenic group A Streptococcus (GAS) within nonphagocytic cells. After escaping from endosomes into the cytoplasm, GAS became enveloped by autophagosome-like compartments and were killed upon fusion of these compartments with lysosomes. In autophagy-deficient Atg5-/- cells, GAS survived, multiplied, and were released from the cells. Thus, the autophagic machinery can act as an innate defense system against invading pathogens.

Autophagy degrades unnecessary organelles and misfolded protein aggregates, as well as cytoplasm-invading bacteria. Nevertheless, the bacteria Listeria monocytogenes efficiently escapes autophagy. We show here that recruitment of the Arp2/3 complex and Ena/VASP, via the bacterial ActA protein, to the bacterial surface disguises the bacteria from autophagic recognition, an activity that is independent of the ability to mediate bacterial motility. L. monocytogenes expressing ActA mutants that lack the ability to recruit the host proteins initially underwent ubiquitylation, followed by recruitment of p62 (also known as SQSTM1) and LC3, before finally undergoing autophagy. The ability of ActA to mediate protection from ubiquitylation was further demonstrated by generating aggregate-prone GFP-ActA-Q79C and GFP-ActA-170(*) chimaeras, consisting of GFP (green fluorescent protein), the ActA protein and segments of polyQ or Golgi membrane protein GCP170 (ref. 6). GFP-ActA-Q79C and GFP-ActA-170(*) formed aggregates in the host cell cytoplasm, however, these ActA-containing aggregates were not targeted for association with ubiquitin and p62. Our findings indicate that ActA-mediated host protein recruitment is a unique bacterial disguise tactic to escape from autophagy.

Porphyromonas gingivalis fimA gene encoding fimbrillin, a subunit of fimbriae, has been classified into 5 genotypes (types I to V) based on their nucleotide sequences. Here, we investigated the relationship between the prevalence of these fimA genotypes and periodontal health status in adults. Dental plaque specimens obtained from 380 periodontally healthy adults and 139 periodontitis patients were analyzed by the PCR method. P. gingivalis was detected in 36.8% of the healthy subjects and in 87.1% of the periodontitis patients. Among the P. gingivalis-positive healthy adults, the most prevalent fimA type was type I (76.1%), followed by type V. In contrast, a majority of the periodontitis patients carried type II fimA organisms (66.1%), followed by type IV. The univariate analysis illustrated that periodontitis was associated with the occurrences of type I fimA (OR 0.16), type II (OR 44.44), type III (1.96), type IV (13.87), and type V (1.40). These findings clearly indicate that there are both disease-associated and non-disease-associated strains of P. gingivalis, and that their infectious traits influencing periodontal health status could be differentiated based on the clonal variation of fimA genes.