Why Clusters Instead of Chains

Mark A. Crislip, MD

Disclosures

June 07, 2021

The patient has a month of progressive failure to thrive and a cough. Workup is negative as an outpatient, and he is given a week of prednisone for RAD. He improves, then worsens.

Seen in the ER, he is afebrile and has a negative exam except for a murmur from his 5-year-old bioprosthetic valve. The worry is an occult malignancy, so among other studies, he has a pan-scan.

At the same time, blood cultures drawn the preceding day are growing gram-positive cocci in clusters.

The CT looked like classic embolic lesions to the kidney.

So, I said it is prosthetic valve endocarditis, probably coagulase-negative Staphylococcus or, given how indolent his infection is, a Micrococcus, which forms tetrads and kind of cluster. Although the preliminary molecular ID said none of the above, it is not always correct.

But what else causes gram-positive clusters?

Gemella morbillorum.

That forms clusters? Yep. Pairs, short chains, or clusters.

Are there other pathogenic gram-positive cocci that make clusters? I can't find it.

Gemella endocarditis is rare, with 65 cases in the most recent review. I do not think I have ever seen a case. A TEE showed nothing evil, but I suspect all his vegetation had moved on to his kidneys.

He has done well on penicillin and a short course of gentamicin.

But why do some gram-positives grow in clusters and others grow in chains?

Streptococci grow in one plane because they split down the middle, but with Staphylococcus,

The organisms appeared to divide in three alternating perpendicular planes, with sister cells remaining attached to each other after division. The resulting point of attachment was usually not exactly at the point corresponding to the center of the previous septal disk. Moreover, sister cells often changed position with respect to one another while still remaining attached. These factors are apparently responsible for the irregularity of staphylococcal clumps. Studies with penicillin and the examination of thin sections in the electron microscope confirm the conclusion, based upon light microscopy, that successive divisions in S. aureus occur in perpendicular planes.

It remains round throughout replication, unlike other bacteria which elongate, as

S. aureus lacks an apparent elongasome machinery.

That was 1976. Nothing from 1976 has stood the test of time. Now?

Although this mode of division was proposed over four decades ago, the molecular mechanism that ensures this geometry of division has remained elusive S. aureus cells do not regularly divide in three alternating perpendicular planes as previously thought. Imaging of the division shows that a plane of division is always perpendicular to the previous one, avoiding bisection of the nucleoid, which segregates along an axis parallel to the closing septum. However, one out of the multiple planes perpendicular to the septum which divide the cell in two identical halves can be used in daughter cells, irrespective of its orientation in relation to the penultimate division plane. Therefore, division in three orthogonal planes is not the rule in S. aureus.

as

…although a plane of division is always perpendicular to the previous one, it is not necessarily perpendicular to the penultimate division plane. As a consequence, the majority of S. aureus cells do not divide in three alternating orthogonal planes.

There is even a cool video, with a paltry 254 views, demonstrating how S aureus is a cluster-bug. There are 9000 ID docs in the US; you would think more would have been curious about why some gram-positives are chains, others clusters, and found the video.

There are similar studies on Micrococcus but not Gemella.

Those studies explain what Staphylococcus does, not why. Is there a benefit to three-dimensional replication? Insert NSFW comment of your own devising here.

The non-standard cross-section of the septum in S. aureus distinguishes it from other model organisms and indicates that not all peptidoglycan insertion occurs at the leading edge of the septum in this species prompting the development of a new model for how peptidoglycan is synthesized during the cell cycle). This is likely advantageous to the bacteria, enabling more biosynthetic enzymes to work on the cell wall without steric hindrance.

I assume every function in an organism has an evolved reason, so an improved peptidoglycan synthesis works for me.

But for S aureus, I wonder if clustering has a more pathogenic/malign origin. As to Gemella? All I can find is that it is a cousin of Staphylococcus, in the order of Bacillales and the family of Staphylococcaceae. So perhaps something similar.

Rationalization

Youssef D, Youssef I, Marroush TS, Sharma M. Gemella endocarditis: A case report and a review of the literature. Avicenna J Med. 2019;9:164-168. Source

Tzagoloff H, Novick R. Geometry of cell division in Staphylococcus aureus. J Bacteriol. 1977;129:343-350. Source

Lund VA, Wacnik K, Turner RD, et al. Molecular coordination of Staphylococcus aureus cell division. eLife. 2018;7:e32057. Source

Saraiva BM, Sorg M, Pereira AR, et al. Reassessment of the distinctive geometry of Staphylococcus aureus cell division. Nat Commun. 2020;11:4097. Source

Geometry of Staphylococcus aureus cell division (video)

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About Dr Mark Crislip
Mark A. Crislip, MD, has been practicing infectious diseases in Portland, Oregon, since 1990. He is nobody from nowhere but has an enormous ego that leads him to think someone might care about what he has to say about infectious diseases. He has been blogging on the most endlessly fascinating specialty in all of medicine since 2008 and has yet to run out of material. Or perhaps he is just a slow learner. His multimedia empire is at edgydoc.com.

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