Fine Read­ing: Auto­pha­gy & the Cy­toskele­ton

New Links Re­vealed By In­tra­cel­lu­lar Pathogens

by Elio

Life in­side cells of the im­mune sys­tem presents a spe­cial chal­lenge to path­o­genic bac­te­ria. Some are killed af­ter be­ing taken up, oth­ers sur­vive. One fa­vorite mech­a­nism used by Shigella, Lis­te­ria, and Rick­ettsia, among oth­ers, is to es­cape from the phago­cytic vac­uole into the cy­to­plasm. This avoids the ac­tion of en­zymes from the lyso­somes that would oth­er­wise fuse with the bac­te­ria-con­tain­ing vac­uole. Once in the cy­tosol, the in­vaders en­joy what seems to be a rich and care­free ex­is­tence.

Thin sec­tion of a Lis­te­ria-in­fected macro phage. A sin­gle Lis­te­ria is lo­cated at the tip of a pro­jec­tion from the macrophage cell sur­face and be­hind it a long fil­a­men­tous tail com­posed of actin fibers. Source

But how do they in­fect new host cells? In­stead of sim­ply sit­ting idly, these bac­te­ria re­cruit host actin, which in poly­mer­iz­ing pushes them around. When the mov­ing bac­te­ria hit the host cell mem­brane, they en­ter into pro­tru­sions that can pen­e­trate into an ad­ja­cent cell. This has been the con­ven­tional story. The bug wins, or so it would seem. What does the host cell do about it? It has been dis­cov­ered re­cently that the cells re­spond to these gym­nas­tics by en­cas­ing the bac­te­ria in cages of a cy­toskele­tal pro­tein called septin. Now the bac­te­ria can be dealt with by the au­tophagy sys­tem of the cell. The chore­og­ra­phy be­tween host and par­a­site con­tin­ues.

One of the most sat­is­fy­ing as­pects of cur­rent day Mi­cro­bi­ol­ogy is how study­ing pathogens has con­tributed to our un­der­stand­ing of the host cell. Just like phages have helped un­der­stand bac­te­ria, mam­malian pathogens have helped elu­ci­date the in­ner work­ings of their host.