Antigenic variation impacts gonococcal lifestyle and antibiotic tolerance by modulating interbacterial forces
Bibliographic record
Abstract
Abstract Type 4 pili (T4P) are multifunctional filaments involved in adhesion, surface motility, colony formation, and horizontal gene transfer. These extracellular polymers are surface-exposed and, therefore, act as antigens. The human pathogen Neisseria gonorrhoeae uses pilin antigenic variation to escape immune surveillance, yet it is unclear how antigenic variation impacts other functions of T4P. Here, we addressed this question by replacing the major pilin of a laboratory strain of N. gonorrhoeae with pilins from clinical isolates. Structural predictions reveal filament features that vary from one strain to the next, with the potential to impact pilus:pilus interactions. Using a combination of laser tweezers, electron microscopy, and advanced image analysis, we explore the phenotypic consequences of these structural changes. We reveal that strains differing only in their major pilin sequence vary substantially in their attractive forces, which we attribute to variations in the stereochemistry of the T4P filament. In liquid culture, strongly interacting bacteria form colonies while weakly interacting bacteria retain a planktonic lifestyle. We show that lifestyle strongly affects growth kinetics and antibiotic tolerance. In the absence of external stresses, planktonic bacteria grow faster than colony-forming bacteria. In the presence of the antibiotics ceftriaxone and ciprofloxacin, the killing kinetics indicate strongly increased tolerance of colony-forming strains. We propose that pilin antigenic variation produces a mixed population containing variants optimized for growth, colonization, or survivability under external stress. Different environments select different variants, ensuring the survival and reproduction of the population as a whole. Significance statement Neisseria are highly successful human pathogens that continuously vary their surface structures to escape immune surveillance. Antigenic variation of the major pilin subunit causes variations of the structure of the Type 4 pilus, a surface exposed virulence factor. Here, we investigate the effect of pilin antigenic variation on bacterial lifestyle and tolerance against antibiotics. We find that pilin antigenic variation causes changes in the physical interactions between the bacteria, resulting in distinct aggregating and planktonic phenotypes. During treatment with antibiotics, aggregating strains are more tolerant than planktonic strains by an order of magnitude. Since tolerance tends to facilitate resistance development, pilin antigenic variation reduces the efficiency of antibiotic treatment.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".