Health Research in Honey Bees

From Bee Craft: July 2009

Professor Jurgen Tautz and Olaf Gimple

Integrative biology which has practical relevance


Fig 1. The economic ranking of cattle, pigs, honey bees and poultry
(from The Buzz about Bees, J Tautz and H Heilmann, Springer, Heidelberg 2008)

IT IS widely unknown that the honey bee (Apis mellifera) is the third most important domestic animal in Europe, after cattle and pigs and before poultry (Fig 1), not because of its honey and wax production, but because of its invaluable contribution to the fertilization of our fruit trees and numerous other crop plants. Moreover, honey bees are indispensable for maintaining the diversity of wild flowers.

Hence the alarmingly high bee mortality, partly of catastrophic dimensions, as presently observed in Germany, Spain and the USA, is a major economical and scientific challenge for honey bee health research.


Honey bees undergo a number of developmental stages before finally emerging as an adult bee: egg, larva, prepupa, pupa and imago. Larvae are fed by nurse bees for about six days and gain 1000 times the egg weight during this period. At the prepupal stage, the wax cells are capped and the metamorphosis of the pupae goes on for about 12 days after which adult bees emerge from the cells (Fig 2A).

Honey bees are unique among animals as they create and control the environment under which they are living. Two factors are outstanding: honey bee larvae are fed with a mixture of glandular secretions (royal jelly) produced by nurse bees and honey bee pupae are kept at a constant temperature of between 35 °C and 36 °C, very close to human body temperature.


Fig 2. In vivo and in vitro reared bee larvae and pupae:
A) Natural brood comb with some artificially uncapped cells to view prepupae and pupae
B) Bee larvae (2-4 days old) reared in tissue culture plates (24 wells) on a mixed diet consisting of royal jelly, glucose, fructose and yeast extract

One important prerequisite for analysing the processes which are initiated by microbial infections was the establishment of a system for breeding bees individually under pathogen-free conditions, in vitro. This is not a trivial achievement as raising brood in a bee hive is a highly complex process performed by a large proportion of the colony members.

Freshly hatched larvae were collected from a comb and transferred into the wells of microtiter plates (Fig 2B). The larvae were then maintained in an incubator at a constant temperature (35 °C). Under natural conditions in a bee hive, the cells are capped at this stage. As a consequence, the pupae are no longer supplied with food.

We mimicked this situation by transferring the sixth-instar larvae from the tissue culture plates to horizontally oriented Eppendorf micro test tubes sealed with cotton (Figs 3C/D). After 12 to 14 days, pupae had successfully developed into adult worker bees.


Fig 3C/D. Bee pupae kept in Eppendorf micro test tubes sealed with cotton wool. Larvae and pupae are kept at 35 °C

As social insects, honey bees spend most of their lives densely crowded (about 50,000 individuals) inside their nest in constant, close contact to each other (Fig 4). Such extreme living conditions enforced the evolution of very effective defence strategies against pathogens and parasites.

Honey bees, like all invertebrates, lack an adaptive immune system. Instead they have developed an efficient strategy for combating microbial infections, called an ‘innate immune response’. Generally six lines of defence are utilised:


a physical barriers, eg, the cuticle and the epithelium of the gut

b the behaviour of the bees such as the removal of diseased animals from the colony

c a cellular immune response (phagocytosis, nodule formation, encapsulation and phenoloxidase activation)

d humoral immune response, ie, simultaneous induction of a broad spectrum of antimicrobial peptides upon pathogen infection

e the construction and microclimate inside the nest

f swarming behaviour.


Fig 4. Worker honey bees on freshly built combs n = cells filled with nectar p = cells filled with pollen e = empty cells

The cooperation between cellular and humoral immune reactions in a well-balanced network is necessary for a successful defence against invading pathogens.

We have begun to study the details of each of these lines of defence, how they are initiated by the pathogens and how they interact, starting from the socio-physiology of the bee colony to the molecular biology of individual bees. A better understanding of these mechanisms would offer a chance to strengthen the bee’s immune response and to improve bee health.


We thank Professor H Beier, Professor HJ Gross,

Dr J Reinders, Dr S Albert and K Randolt for their continuing cooperation.

[BEEgroup, Biozentrum, Universitat Wurzburg, Am Hubland, D-97074 Wurzburg]

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